NM_012431.3(SEMA3E):c.1172A>T (p.Tyr391Phe) AND CHARGE association

Clinical significance:Uncertain significance (Last evaluated: Mar 31, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001037725.2

Allele description [Variation Report for NM_012431.3(SEMA3E):c.1172A>T (p.Tyr391Phe)]

NM_012431.3(SEMA3E):c.1172A>T (p.Tyr391Phe)

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.1172A>T (p.Tyr391Phe)
HGVS:
  • NC_000007.14:g.83400222T>A
  • NG_021242.2:g.253942A>T
  • NM_001178129.2:c.992A>T
  • NM_012431.3:c.1172A>TMANE SELECT
  • NP_001171600.1:p.Tyr331Phe
  • NP_036563.1:p.Tyr391Phe
  • LRG_1287t1:c.1172A>T
  • LRG_1287:g.253942A>T
  • LRG_1287p1:p.Tyr391Phe
  • NC_000007.13:g.83029538T>A
  • NM_012431.2:c.1172A>T
Protein change:
Y331F
Links:
dbSNP: rs753965043
NCBI 1000 Genomes Browser:
rs753965043
Molecular consequence:
  • NM_001178129.2:c.992A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012431.3:c.1172A>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
SCV001201153Invitaecriteria provided, single submitter
Uncertain significance
(Mar 31, 2020)
germlineclinical testing

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

SCV001528756Baylor Geneticscriteria provided, single submitter
Uncertain significance
(Jun 14, 2018)
paternalclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedpaternalyesnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

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 Invitae, SCV001201153.2

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

Description

This sequence change replaces tyrosine with phenylalanine at codon 391 of the SEMA3E protein (p.Tyr391Phe). The tyrosine residue is highly conserved and there is a small physicochemical difference between tyrosine and phenylalanine. This variant is present in population databases (rs753965043, ExAC 0.1%). This variant has not been reported in the literature in individuals with SEMA3E-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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

From Baylor Genetics, SCV001528756.1

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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

Last Updated: Nov 27, 2021

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