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NM_005445.4(SMC3):c.2653A>C (p.Asn885His) AND Cornelia de Lange syndrome 3

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 19, 2020
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:
RCV002470380.1

Allele description [Variation Report for NM_005445.4(SMC3):c.2653A>C (p.Asn885His)]

NM_005445.4(SMC3):c.2653A>C (p.Asn885His)

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.2653A>C (p.Asn885His)
HGVS:
  • NC_000010.11:g.110601645A>C
  • NG_012217.1:g.38955A>C
  • NM_005445.4:c.2653A>CMANE SELECT
  • NP_005436.1:p.Asn885His
  • NP_005436.1:p.Asn885His
  • LRG_774t1:c.2653A>C
  • LRG_774:g.38955A>C
  • LRG_774p1:p.Asn885His
  • NC_000010.10:g.112361403A>C
  • NM_005445.3:c.2653A>C
Protein change:
N885H
Molecular consequence:
  • NM_005445.4:c.2653A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cornelia de Lange syndrome 3 (CDLS3)
Synonyms:
CORNELIA DE LANGE SYNDROME 3 WITH OR WITHOUT MIDLINE BRAIN DEFECTS
Identifiers:
MONDO: MONDO:0012555; MedGen: C1853099; Orphanet: 199; OMIM: 610759

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002767172Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Oct 19, 2020) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002767172.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as VUS -3B. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. Loss of function and dominant negative are both suggested mechanisms. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from asparagine to histidine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v3) (1 heterozygote, 0 homozygotes). (I) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0600 - Variant is located in the annotated Smc domain (NCBI, PDB). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited by trio analysis. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 5, 2023