NM_005445.4(SMC3):c.1942A>G (p.Met648Val) AND Intellectual disability

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 9, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000721938.2

Allele description

NM_005445.4(SMC3):c.1942A>G (p.Met648Val)

Gene:

SMC3:structural maintenance of chromosomes 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q25.2

Genomic location:

Preferred name:

NM_005445.4(SMC3):c.1942A>G (p.Met648Val)

HGVS:

NC_000010.11:g.110593202A>G
NG_012217.1:g.30512A>G
NM_005445.4:c.1942A>GMANE SELECT
NP_005436.1:p.Met648Val
NP_005436.1:p.Met648Val
LRG_774t1:c.1942A>G
LRG_774:g.30512A>G
LRG_774p1:p.Met648Val
NC_000010.10:g.112352960A>G
NM_005445.3:c.1942A>G

Protein change:

M648V

Links:

dbSNP: rs886041239

NCBI 1000 Genomes Browser:

rs886041239

Molecular consequence:

NM_005445.4:c.1942A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Intellectual disability
Synonyms:: Intellectual functioning disability; intellectual disabilities; Intellectual developmental disorder
Identifiers:: MONDO: MONDO:0001071; MeSH: D008607; MedGen: C3714756; Human Phenotype Ontology: HP:0001249

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000852015	Medical Genetics Lab, Policlinico S. Orsola.Malpighi	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 9, 2018)	de novo	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000852015

Medical Genetics Lab, Policlinico S. Orsola.Malpighi

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 9, 2018)

de novo

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	1	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Medical Genetics Lab, Policlinico S. Orsola.Malpighi, SCV000852015.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		1	not provided	not provided	clinical testing	not provided

Description

The Met648Val variant in SMC3 is extremely rare (never reported in GnomAD exomes and genomes) and missense variants of this gene are a known cause of disease. Furthermore, this variant is de novo in the patient and there is no family history of the disease. On the other hand, prediction scores are conflicting (MutationTaster: disease-causing; SIFT: tolerated) and the clinical picture of this patient is not reminiscent of Cornelia de Lange syndrome. We interpret Met648Val as a likely pathogenic variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Feb 25, 2025

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