NM_001005273.3(CHD3):c.3563C>G (p.Ala1188Gly) AND Snijders Blok-Campeau syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 22, 2023
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:: RCV003458982.2

Allele description [Variation Report for NM_001005273.3(CHD3):c.3563C>G (p.Ala1188Gly)]

NM_001005273.3(CHD3):c.3563C>G (p.Ala1188Gly)

Gene:

CHD3:chromodomain helicase DNA binding protein 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_001005273.3(CHD3):c.3563C>G (p.Ala1188Gly)

HGVS:

NC_000017.11:g.7903339C>G
NG_135423.1:g.749C>G
NG_139698.1:g.141C>G
NM_001005271.3:c.3740C>G
NM_001005273.3:c.3563C>GMANE SELECT
NM_005852.4:c.3563C>G
NP_001005271.2:p.Ala1247Gly
NP_001005273.1:p.Ala1188Gly
NP_005843.2:p.Ala1188Gly
NC_000017.10:g.7806657C>G

Protein change:

A1188G

Molecular consequence:

NM_001005271.3:c.3740C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001005273.3:c.3563C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005852.4:c.3563C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Snijders Blok-Campeau syndrome
Synonyms:: INTELLECTUAL DEVELOPMENTAL DISORDER WITH MACROCEPHALY, SPEECH DELAY, AND DYSMORPHIC FACIES
Identifiers:: MONDO: MONDO:0032600; MedGen: C4748701; OMIM: 618205

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004177046	Clinical Genomics Laboratory, Washington University in St. Louis	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 22, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004177046

Clinical Genomics Laboratory, Washington University in St. Louis

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 22, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Clinical Genomics Laboratory, Washington University in St. Louis, SCV004177046.1

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

Description

The CHD3 c.3563C>G (p.Ala1188Gly) variant, to our knowledge, has not been reported in the medical literature and is only observed on 1/251,474 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant occurs in the helicase domain in a region with significant pathogenic/likely pathogenic variant clustering (Mutscore; Quinodoz M et al., PMID: 35120630) immediately upstream of a region that is enriched for pathogenic variation across highly related chromodomain proteins (PER viewer; Pérez-Palma E et al., PMID: 31871067), but computational predictors are uncertain as to the impact of this variant on CHD3 function. Additionally, another variant in the same codon, c.3562G>A (p.Ala1188Thr), is classified as likely pathogenic in ClinVar (Variation ID: 1710244). However, due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.

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

Last Updated: Jun 23, 2024

ClinVar

Relating variation to medicine