U.S. flag

An official website of the United States government

NM_001083116.3(PRF1):c.449C>A (p.Ser150Ter) AND Familial hemophagocytic lymphohistiocytosis

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 8, 2023
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:
RCV003331403.1

Allele description [Variation Report for NM_001083116.3(PRF1):c.449C>A (p.Ser150Ter)]

NM_001083116.3(PRF1):c.449C>A (p.Ser150Ter)

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.449C>A (p.Ser150Ter)
HGVS:
  • NC_000010.11:g.70600454G>T
  • NG_009615.1:g.7322C>A
  • NM_001083116.3:c.449C>AMANE SELECT
  • NM_005041.6:c.449C>A
  • NP_001076585.1:p.Ser150Ter
  • NP_001076585.1:p.Ser150Ter
  • NP_005032.2:p.Ser150Ter
  • LRG_94t1:c.449C>A
  • LRG_94:g.7322C>A
  • LRG_94p1:p.Ser150Ter
  • NC_000010.10:g.72360210G>T
  • NM_001083116.1:c.449C>A
Protein change:
S150*
Molecular consequence:
  • NM_001083116.3:c.449C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_005041.6:c.449C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Familial hemophagocytic lymphohistiocytosis (FHL)
Synonyms:
Hemophagocytic lymphohistiocytosis; Familial erythrophagocytic lymphohistiocytosis; Familial histiocytic reticulosis; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015541; MedGen: C0272199; OMIM: PS267700

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004038415Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Aug 8, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Characterisation of diverse PRF1 mutations leading to decreased natural killer cell activity in North American families with haemophagocytic lymphohistiocytosis.

Molleran Lee S, Villanueva J, Sumegi J, Zhang K, Kogawa K, Davis J, Filipovich AH.

J Med Genet. 2004 Feb;41(2):137-44. No abstract available.

PubMed [citation]
PMID:
14757862
PMCID:
PMC1735659

Aberrant maturation of mutant perforin underlies the clinical diversity of hemophagocytic lymphohistiocytosis.

Risma KA, Frayer RW, Filipovich AH, Sumegi J.

J Clin Invest. 2006 Jan;116(1):182-92. Epub 2005 Dec 22.

PubMed [citation]
PMID:
16374518
PMCID:
PMC1319223
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004038415.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: PRF1 c.449C>A (p.Ser150X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2e-05 in 251434 control chromosomes (gnomAD). c.449C>A has been reported in the literature in individuals affected with Familial Hemophagocytic Lymphohistiocytosis (Molleran_2004, Risma_2005). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 14757862, 16374518, 32696691). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Feb 20, 2024