Summary Statistics:
Gene Score: 4S
Relevance to Autism
A de novo likely gene disruptive (LGD) variant in SMC3 was identified in an ASD proband from the Autism Simplex Collection in Stessman et al., 2017. Mutations in the SMC3 gene are associated with a form of Cornelia de Lange syndrome (Cornelia de Lange syndrome 3; OMIM 610759) (Deardorff et al., 2007; Gil-Rodrguez et al., 2015). Phenotypic characterization of 16 patients with Cornelia de Lange-like features caused by SMC3 variants in Gil-Rodrguez et al., 2015 demonstrated that, while intellectual disability was a prominent feature, behavioral problems were less frequently reported (1 individual presented with autism, whereas another presented with autistic features; poor eye contact, attention deficit disorder, aggression, and self-injurious behavior were also observed).
Molecular Function
Central component of cohesin, a complex required for chromosome cohesion during the cell cycle.
References
Primary
The contribution of de novo coding mutations to autism spectrum disorder
ASD
Support
Whole genome sequencing analysis identifies sex differences of familial pattern contributing to phenotypic diversity in autism
ASD
Support
Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort.
ASD
Support
Heterozygous loss-of-function SMC3 variants are associated with variable growth and developmental features
DD
ASD, ADD, ADHD, ID, epilepsy/seizures
Support
Genomic diagnosis for children with intellectual disability and/or developmental delay.
ID
Support
De novo heterozygous mutations in SMC3 cause a range of Cornelia de Lange syndrome-overlapping phenotypes.
Cornelia de Lange syndrome-3 (CDLS3)
Support
DD, ID, epilepsy/seizures
Support
Large-scale discovery of novel genetic causes of developmental disorders.
DD
Support
Integrating de novo and inherited variants in 42
ASD
Support
Genomic landscape of rare variants in a Chinese autism cohort and discovery of novel risk genes.
ASD
Support
Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder
ASD
Support
Genomic insights from a deeply phenotyped highly consanguineous neurodevelopmental disorders cohort
DD, ID
Support
Diagnostic Yields of Trio-WES Accompanied by CNVseq for Rare Neurodevelopmental Disorders.
DD
Highly Cited
Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation.
Cornelia de Lange syndrome-3 (CDLS3)
Recent Recommendation
Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement.
Cornelia de Lange syndrome-3 (CDLS3)
Recent Recommendation
Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.
ASD
GEN877R001
missense_variant
c.2413C>T
p.Arg805Cys
De novo
Simplex
GEN877R002
frameshift_variant
c.2412dup
p.Arg805SerfsTer13
De novo
Simplex
GEN877R003
frameshift_variant
TGAAAAGAA>TGAA
De novo
GEN877R004
missense_variant
c.3563G>C
p.Gly1188Ala
De novo
GEN877R005
missense_variant
c.283G>A
p.Glu95Lys
De novo
GEN877R006
inframe_deletion
c.1464_1466del
p.Glu488del
De novo
GEN877R007
missense_variant
c.1892T>C
p.Leu631Pro
Unknown
Simplex
GEN877R008
frameshift_variant
c.1071_1074del
p.Glu358AsnfsTer44
De novo
GEN877R009
missense_variant
c.324G>C
p.Gln108His
Unknown
GEN877R010
inframe_deletion
c.2062_2064del
p.Glu688del
De novo
GEN877R011
missense_variant
c.2372T>G
p.Leu791Trp
De novo
GEN877R012
missense_variant
c.3035A>T
p.Lys1012Ile
De novo
Multiplex
GEN877R013
inframe_deletion
c.2005_2007del
p.Tyr669del
De novo
GEN877R014
inframe_deletion
c.3002_3004del
p.Ile1001del
De novo
Simplex
GEN877R015
splice_site_variant
c.430-1G>T
De novo
GEN877R016
frameshift_variant
c.461dup
p.Arg155GlufsTer12
Unknown
GEN877R017
stop_gained
c.661C>T
p.Arg221Ter
Familial
Maternal
GEN877R018
stop_gained
c.778C>T
p.Gln260Ter
De novo
GEN877R019
stop_gained
c.1078C>T
p.Arg360Ter
Familial
Paternal
GEN877R020
frameshift_variant
c.1474_1478del
p.Lys492AlafsTer5
De novo
GEN877R021
frameshift_variant
c.1539del
p.Asn513LysfsTer4
Unknown
GEN877R022
stop_gained
c.1561C>T
p.Arg521Ter
Unknown
GEN877R023
stop_gained
c.2899C>T
p.Arg967Ter
De novo
GEN877R024
frameshift_variant
c.3646_3647dup
p.Gly1217MetfsTer39
Unknown
GEN877R025
copy_number_loss
De novo
GEN877R026
copy_number_loss
De novo
GEN877R027
copy_number_loss
Unknown
Not maternal
GEN877R028
copy_number_loss
Familial
Paternal
GEN877R029
missense_variant
c.3517A>G
p.Thr1173Ala
De novo
GEN877R030
missense_variant
c.707G>C
p.Arg236Pro
Unknown
GEN877R031
frameshift_variant
c.1021_1025delinsC
p.Lys342AsnfsTer12
De novo
Simplex
No Common Variants Available
10
Deletion-Duplication
7
No Interactions Available
