NM_012431.3(SEMA3E):c.371A>G (p.His124Arg) AND CHARGE syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 26, 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:: RCV001059620.7

Allele description [Variation Report for NM_012431.3(SEMA3E):c.371A>G (p.His124Arg)]

NM_012431.3(SEMA3E):c.371A>G (p.His124Arg)

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.371A>G (p.His124Arg)

HGVS:

NC_000007.14:g.83466567T>C
NG_021242.2:g.187597A>G
NM_001178129.2:c.191A>G
NM_012431.3:c.371A>GMANE SELECT
NP_001171600.1:p.His64Arg
NP_036563.1:p.His124Arg
LRG_1287t1:c.371A>G
LRG_1287:g.187597A>G
LRG_1287p1:p.His124Arg
NC_000007.13:g.83095883T>C
NM_012431.2:c.371A>G

Protein change:

H124R

Links:

dbSNP: rs1487949587

NCBI 1000 Genomes Browser:

rs1487949587

Molecular consequence:

NM_001178129.2:c.191A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_012431.3:c.371A>G - 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

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Protein
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Gene ID:3773939

Gene
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Gene ID:3255530

Gene
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Gene ID:3914061

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001224247	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 26, 2020)	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

SCV001224247

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 26, 2020)

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 Invitae, SCV001224247.5

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

Description

This sequence change replaces histidine with arginine at codon 124 of the SEMA3E protein (p.His124Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SEMA3E-related conditions. This variant is not present in population databases (ExAC no frequency).

#	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 2, 2024

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