NM_017837.4(PIGV):c.115G>A (p.Glu39Lys) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Aug 16, 2022
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001662530.17

Allele description [Variation Report for NM_017837.4(PIGV):c.115G>A (p.Glu39Lys)]

NM_017837.4(PIGV):c.115G>A (p.Glu39Lys)

Gene:

PIGV:phosphatidylinositol glycan anchor biosynthesis class V [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.11

Genomic location:

Preferred name:

NM_017837.4(PIGV):c.115G>A (p.Glu39Lys)

HGVS:

NC_000001.11:g.26794149G>A
NG_028133.1:g.11187G>A
NM_001202554.2:c.115G>A
NM_001374478.1:c.115G>A
NM_001374480.1:c.115G>A
NM_001374481.1:c.115G>A
NM_001374482.1:c.115G>A
NM_001374483.1:c.-267G>A
NM_001374484.1:c.115G>A
NM_001374485.1:c.115G>A
NM_001374486.1:c.78+3256G>A
NM_017837.4:c.115G>AMANE SELECT
NP_001189483.1:p.Glu39Lys
NP_001189483.1:p.Glu39Lys
NP_001361407.1:p.Glu39Lys
NP_001361409.1:p.Glu39Lys
NP_001361410.1:p.Glu39Lys
NP_001361411.1:p.Glu39Lys
NP_001361413.1:p.Glu39Lys
NP_001361414.1:p.Glu39Lys
NP_060307.2:p.Glu39Lys
NP_060307.2:p.Glu39Lys
NC_000001.10:g.27120640G>A
NM_001202554.1:c.115G>A
NM_001202554.1:c.115G>A
NM_017837.3:c.115G>A
NR_164651.1:n.613G>A
NR_164652.1:n.491G>A

Protein change:

E39K

Links:

dbSNP: rs369275802

NCBI 1000 Genomes Browser:

rs369275802

Molecular consequence:

NM_001374483.1:c.-267G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001374486.1:c.78+3256G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001202554.2:c.115G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374478.1:c.115G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374480.1:c.115G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374481.1:c.115G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374482.1:c.115G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374484.1:c.115G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374485.1:c.115G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_017837.4:c.115G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_164651.1:n.613G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164652.1:n.491G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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cytochrome c oxidase subunit I (mitochondrion) [Caryanda elegans]
cytochrome c oxidase subunit I (mitochondrion) [Caryanda elegans]
gi|1331215849|ref|YP_009454599.1|

Protein
hypothetical protein, conserved [Leishmania donovani]
hypothetical protein, conserved [Leishmania donovani]
gi|398017961|ref|XP_003862167.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000617986	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Jun 22, 2018)	germline	clinical testing	Citation Link,
SCV001880188	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics criteria)	Uncertain significance (Mar 19, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002142336	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 16, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000617986

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Jun 22, 2018)

germline

clinical testing

Citation Link,

SCV001880188

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics criteria)

Uncertain significance
(Mar 19, 2021)

unknown

clinical testing

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

SCV002142336

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 16, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV000617986.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Athena Diagnostics, SCV001880188.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV002142336.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 39 of the PIGV protein (p.Glu39Lys). This variant is present in population databases (rs369275802, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PIGV-related conditions. ClinVar contains an entry for this variant (Variation ID: 449659). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 7, 2024

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