NM_000430.4(PAFAH1B1):c.958A>G (p.Ile320Val) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Feb 1, 2024
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:: RCV001545406.8

Allele description [Variation Report for NM_000430.4(PAFAH1B1):c.958A>G (p.Ile320Val)]

NM_000430.4(PAFAH1B1):c.958A>G (p.Ile320Val)

Gene:

PAFAH1B1:platelet activating factor acetylhydrolase 1b regulatory subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.3

Genomic location:

Preferred name:

NM_000430.4(PAFAH1B1):c.958A>G (p.Ile320Val)

HGVS:

NC_000017.11:g.2676562A>G
NG_009799.1:g.87934A>G
NM_000430.4:c.958A>GMANE SELECT
NP_000421.1:p.Ile320Val
NC_000017.10:g.2579856A>G
NM_000430.3:c.958A>G

Protein change:

I320V

Links:

dbSNP: rs144659773

NCBI 1000 Genomes Browser:

rs144659773

Molecular consequence:

NM_000430.4:c.958A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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hydroxymethylglutaryl-CoA lyase, mitochondrial-like isoform X1 [Cucurbita maxima...
hydroxymethylglutaryl-CoA lyase, mitochondrial-like isoform X1 [Cucurbita maxima]
gi|1281021653|ref|XP_022995070.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001764732	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Apr 6, 2020)	germline	clinical testing	Citation Link,
SCV002286122	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 1, 2024)	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

SCV001764732

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Apr 6, 2020)

germline

clinical testing

Citation Link,

SCV002286122

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 1, 2024)

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

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

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV001764732.1

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002286122.3

#	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 isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 320 of the PAFAH1B1 protein (p.Ile320Val). This variant is present in population databases (rs144659773, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PAFAH1B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 199020). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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: Sep 29, 2024

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