NM_012431.3(SEMA3E):c.1855C>T (p.Arg619Cys) AND CHARGE association

Clinical significance:Uncertain significance (Last evaluated: Aug 18, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000231032.3

Allele description [Variation Report for NM_012431.3(SEMA3E):c.1855C>T (p.Arg619Cys)]

NM_012431.3(SEMA3E):c.1855C>T (p.Arg619Cys)

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.1855C>T (p.Arg619Cys)
HGVS:
  • NC_000007.14:g.83385314G>A
  • NG_021242.2:g.268850C>T
  • NM_001178129.2:c.1675C>T
  • NM_012431.3:c.1855C>TMANE SELECT
  • NP_001171600.1:p.Arg559Cys
  • NP_036563.1:p.Arg619Cys
  • LRG_1287t1:c.1855C>T
  • LRG_1287:g.268850C>T
  • LRG_1287p1:p.Arg619Cys
  • NC_000007.13:g.83014630G>A
  • NM_012431.2:c.1855C>T
Protein change:
R559C; ARG619CYS
Links:
OMIM: 608166.0002; dbSNP: rs143631464
NCBI 1000 Genomes Browser:
rs143631464
Molecular consequence:
  • NM_001178129.2:c.1675C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012431.3:c.1855C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000289888Invitaecriteria provided, single submitter
Uncertain significance
(Aug 18, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

SEMA3E mutation in a patient with CHARGE syndrome.

Lalani SR, Safiullah AM, Molinari LM, Fernbach SD, Martin DM, Belmont JW.

J Med Genet. 2004 Jul;41(7):e94. No abstract available.

PubMed [citation]
PMID:
15235037
PMCID:
PMC1735828

Dysfunctional SEMA3E signaling underlies gonadotropin-releasing hormone neuron deficiency in Kallmann syndrome.

Cariboni A, André V, Chauvet S, Cassatella D, Davidson K, Caramello A, Fantin A, Bouloux P, Mann F, Ruhrberg C.

J Clin Invest. 2015 Jun;125(6):2413-28. doi: 10.1172/JCI78448. Epub 2015 May 18.

PubMed [citation]
PMID:
25985275
PMCID:
PMC4497752
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000289888.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine with cysteine at codon 619 of the SEMA3E protein (p.Arg619Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs143631464, ExAC 0.02%). This variant has been reported in two brothers with Kallmann syndrome (PMID: 25985275) and an individual with CHARGE syndrome, who inherited the variant from an unaffected parent (PMID: 15235037). ClinVar contains an entry for this variant (Variation ID: 221681). Experimental studies have shown that this missense change disrupts the ability of the protein to prevent cell death in cultured neurons (PMID: 25985275). 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.

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

Last Updated: Nov 6, 2021

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