NM_012431.3(SEMA3E):c.1636C>T (p.Arg546Trp) AND CHARGE syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 18, 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:: RCV002928104.3

Allele description [Variation Report for NM_012431.3(SEMA3E):c.1636C>T (p.Arg546Trp)]

NM_012431.3(SEMA3E):c.1636C>T (p.Arg546Trp)

Gene:

SEMA3E:semaphorin 3E [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q21.11

Genomic location:

Preferred name:

NM_012431.3(SEMA3E):c.1636C>T (p.Arg546Trp)

HGVS:

NC_000007.14:g.83392586G>A
NG_021242.2:g.261578C>T
NM_001178129.2:c.1456C>T
NM_012431.3:c.1636C>TMANE SELECT
NP_001171600.1:p.Arg486Trp
NP_036563.1:p.Arg546Trp
LRG_1287t1:c.1636C>T
LRG_1287:g.261578C>T
LRG_1287p1:p.Arg546Trp
NC_000007.13:g.83021902G>A

Protein change:

R486W

Molecular consequence:

NM_001178129.2:c.1456C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_012431.3:c.1636C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: CHARGE syndrome (CHARGE)
Synonyms:: CHARGE ASSOCIATION--COLOBOMA, HEART ANOMALY, CHOANAL ATRESIA, RETARDATION, GENITAL AND EAR ANOMALIES; Coloboma, heart anomaly, choanal atresia, retardation, genital and ear anomalies; CHARGE association; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008965; MedGen: C0265354; Orphanet: 138; OMIM: 214800

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003262478	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 18, 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

SCV003262478

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 18, 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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003262478.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SEMA3E protein function. ClinVar contains an entry for this variant (Variation ID: 2054579). This variant has not been reported in the literature in individuals affected with SEMA3E-related conditions. This variant is present in population databases (rs781734004, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 546 of the SEMA3E protein (p.Arg546Trp).

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine