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NM_001083116.3(PRF1):c.272C>T (p.Ala91Val) AND PRF1-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 30, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003398509.5

Allele description

NM_001083116.3(PRF1):c.272C>T (p.Ala91Val)

Gene:
PRF1:perforin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q22.1
Genomic location:
Preferred name:
NM_001083116.3(PRF1):c.272C>T (p.Ala91Val)
HGVS:
  • NC_000010.11:g.70600631G>A
  • NG_009615.1:g.7145C>T
  • NM_001083116.3:c.272C>TMANE SELECT
  • NM_005041.5:c.272C>T
  • NM_005041.6:c.272C>T
  • NP_001076585.1:p.Ala91Val
  • NP_005032.2:p.Ala91Val
  • LRG_94t1:c.272C>T
  • LRG_94:g.7145C>T
  • NC_000010.10:g.72360387G>A
  • NM_001083116.1:c.272C>T
  • NM_005041.4:c.272C>T
  • P14222:p.Ala91Val
Protein change:
A91V; ALA91VAL
Links:
UniProtKB: P14222#VAR_050482; OMIM: 170280.0011; dbSNP: rs35947132
NCBI 1000 Genomes Browser:
rs35947132
Molecular consequence:
  • NM_001083116.3:c.272C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005041.6:c.272C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
PRF1-related disorder
Synonyms:
PRF1-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004120359PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jan 30, 2024) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot 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 PreventionGenetics, part of Exact Sciences, SCV004120359.2

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

Description

The PRF1 c.272C>T variant is predicted to result in the amino acid substitution p.Ala91Val. This variant has been studied extensively, but its clinical significance remains unclear. The PRF1 gene variant c.272C>T is found at a high frequency among several control populations (up to 4.6% and in many homozygous individuals; and has been classified as a “neutral polymorphism” (Molleran Lee et al. 2004. PubMed ID: 14757862; Zur Stadt et al. 2004. PubMed ID: 15342365). However, considerable clinical and experimental data support a functional role of the p.Ala91Val variant resulting in reduced cytotoxic activity that may be significant for the pathogenesis of hemophagocytic lymphohistiocytosis and other disorders, including NK/T-Cell lymphomas, in both heterozygous and homozygous carriers of the p.Ala91Val substitution (Voskoboinik et al. 2005. PubMed ID: 15755897; Voskoboinik et al. 2007. PubMed ID: 17475905; Martínez-Pomar et al. 2013. PubMed ID: 23073290; Trambas et al. 2005. PubMed ID: 15741215; Clementi et al. 2002. PubMed ID: 12229880; Santoro et al. 2005. PubMed ID: 15921391; Zhang et al. 2011. PubMed ID: 21881043; Mancebo et al. 2006. PubMed ID: 16956828; House et al. 2015. PubMed ID: 25776844; Manso et al. 2014. PubMed ID: 24632576; Willig et al. 2015. PubMed ID: 25937001, Palterer et al. 2017. PubMed ID: 28863861). Consequently, this allele has also been categorized as either a functional polymorphism or as a risk allele. Due to conflicting reports, the significance of this variant remains uncertain.

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

Last Updated: May 19, 2024