NM_020631.6(PLEKHG5):c.971T>C (p.Ile324Thr) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Apr 14, 2019)

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:
RCV000222151.3

Allele description [Variation Report for NM_020631.6(PLEKHG5):c.971T>C (p.Ile324Thr)]

NM_020631.6(PLEKHG5):c.971T>C (p.Ile324Thr)

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.971T>C (p.Ile324Thr)
HGVS:
  • NC_000001.11:g.6472999A>G
  • NG_007978.1:g.52011T>C
  • NM_001042663.3:c.1082T>C
  • NM_001042664.1:c.971T>C
  • NM_001042665.1:c.971T>C
  • NM_001265592.2:c.1082T>C
  • NM_001265593.1:c.1178T>C
  • NM_001265594.2:c.971T>C
  • NM_020631.6:c.971T>CMANE SELECT
  • NM_198681.3:c.1202T>C
  • NM_198681.4:c.971T>C
  • NP_001036128.2:p.Ile361Thr
  • NP_001036129.1:p.Ile324Thr
  • NP_001036130.1:p.Ile324Thr
  • NP_001252521.2:p.Ile361Thr
  • NP_001252522.1:p.Ile393Thr
  • NP_001252523.1:p.Ile324Thr
  • NP_065682.2:p.Ile324Thr
  • NP_941374.2:p.Ile401Thr
  • NP_941374.3:p.Ile324Thr
  • LRG_262:g.52011T>C
  • NC_000001.10:g.6533059A>G
  • NM_020631.4:c.971T>C
  • p.Ile401Thr
Protein change:
I324T
Links:
dbSNP: rs746862312
NCBI 1000 Genomes Browser:
rs746862312
Molecular consequence:
  • NM_001042663.3:c.1082T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042664.1:c.971T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042665.1:c.971T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265592.2:c.1082T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265593.1:c.1178T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001265594.2:c.971T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020631.6:c.971T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198681.3:c.1202T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198681.4:c.971T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000279989GeneDxcriteria provided, single submitter
Uncertain significance
(Oct 19, 2016)
germlineclinical testing

Citation Link,

SCV001713776Mayo Clinic Laboratories, Mayo Cliniccriteria provided, single submitter
Uncertain significance
(Apr 14, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing

Citations

PubMed

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 GeneDx, SCV000279989.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The I324T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I324T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals; however, Threonine is observed at this position in evolution. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV001713776.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

Last Updated: Oct 25, 2021

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