NM_012431.3(SEMA3E):c.520C>T (p.Pro174Ser) AND CHARGE association

Clinical significance:Uncertain significance (Last evaluated: Jan 19, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_012431.3(SEMA3E):c.520C>T (p.Pro174Ser)]

NM_012431.3(SEMA3E):c.520C>T (p.Pro174Ser)

SEMA3E:semaphorin 3E [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_012431.3(SEMA3E):c.520C>T (p.Pro174Ser)
  • NC_000007.14:g.83418420G>A
  • NG_021242.2:g.235744C>T
  • NM_001178129.2:c.340C>T
  • NM_012431.3:c.520C>TMANE SELECT
  • NP_001171600.1:p.Pro114Ser
  • NP_036563.1:p.Pro174Ser
  • LRG_1287t1:c.520C>T
  • LRG_1287:g.235744C>T
  • LRG_1287p1:p.Pro174Ser
  • NC_000007.13:g.83047736G>A
  • NM_012431.2:c.520C>T
Protein change:
dbSNP: rs1441322114
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001178129.2:c.340C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012431.3:c.520C>T - missense variant - [Sequence Ontology: SO:0001583]


CHARGE association (CHARGE)
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]
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)
SCV000831852Invitaecriteria provided, single submitter
Uncertain significance
(Jan 19, 2018)
germlineclinical 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



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]

Details of each submission

From Invitae, SCV000831852.1

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


This sequence change replaces proline with serine at codon 174 of the SEMA3E protein (p.Pro174Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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

Last Updated: Oct 24, 2021

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