NM_020631.6(PLEKHG5):c.1139C>T (p.Ala380Val) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Jan 16, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000794434.2

Allele description [Variation Report for NM_020631.6(PLEKHG5):c.1139C>T (p.Ala380Val)]

NM_020631.6(PLEKHG5):c.1139C>T (p.Ala380Val)

Gene:
PLEKHG5:pleckstrin homology and RhoGEF domain containing G5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.31
Genomic location:
Preferred name:
NM_020631.6(PLEKHG5):c.1139C>T (p.Ala380Val)
HGVS:
  • NC_000001.11:g.6471630G>A
  • NG_007978.1:g.53380C>T
  • NM_001042663.3:c.1250C>T
  • NM_001042664.1:c.1139C>T
  • NM_001042665.1:c.1139C>T
  • NM_001265592.2:c.1250C>T
  • NM_001265593.1:c.1346C>T
  • NM_001265594.2:c.1139C>T
  • NM_020631.6:c.1139C>TMANE SELECT
  • NM_198681.4:c.1139C>T
  • NP_001036128.2:p.Ala417Val
  • NP_001036129.1:p.Ala380Val
  • NP_001036130.1:p.Ala380Val
  • NP_001252521.2:p.Ala417Val
  • NP_001252522.1:p.Ala449Val
  • NP_001252523.1:p.Ala380Val
  • NP_065682.2:p.Ala380Val
  • NP_941374.3:p.Ala380Val
  • LRG_262:g.53380C>T
  • NC_000001.10:g.6531690G>A
  • NM_020631.4:c.1139C>T
Protein change:
A380V
Links:
dbSNP: rs374286001
NCBI 1000 Genomes Browser:
rs374286001
Molecular consequence:
  • NM_001042663.3:c.1250C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042664.1:c.1139C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042665.1:c.1139C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265592.2:c.1250C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265593.1:c.1346C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265594.2:c.1139C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020631.6:c.1139C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198681.4:c.1139C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Distal spinal muscular atrophy, autosomal recessive 4 (DSMA4)
Identifiers:
MONDO: MONDO:0012608; MedGen: C1970211; Orphanet: 206580; OMIM: 611067
Name:
Charcot-Marie-Tooth disease, recessive intermediate c (CMTRIC)
Synonyms:
CHARCOT-MARIE-TOOTH NEUROPATHY, RECESSIVE INTERMEDIATE C
Identifiers:
MONDO: MONDO:0014154; MedGen: C3809309; Orphanet: 369867; OMIM: 615376

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000933841Invitaecriteria provided, single submitter
Uncertain significance
(Jan 16, 2019)
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

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

Details of each submission

From Invitae, SCV000933841.3

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

Description

This sequence change replaces alanine with valine at codon 380 of the PLEKHG5 protein (p.Ala380Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PLEKHG5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The valine 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.

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

Last Updated: Nov 27, 2021

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