NM_001083116.3(PRF1):c.844AAG[3] (p.Lys285del) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 20, 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:: RCV004034883.1

Allele description [Variation Report for NM_001083116.3(PRF1):c.844AAG[3] (p.Lys285del)]

NM_001083116.3(PRF1):c.844AAG[3] (p.Lys285del)

Gene:

PRF1:perforin 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

10q22.1

Genomic location:

Preferred name:

NM_001083116.3(PRF1):c.844AAG[3] (p.Lys285del)

HGVS:

NC_000010.11:g.70598868TCT[3]
NG_009615.1:g.8899AAG[3]
NM_001083116.3:c.844AAG[3]MANE SELECT
NM_005041.6:c.844AAG[3]
NP_001076585.1:p.Lys285del
NP_005032.2:p.Lys285del
LRG_94t1:c.853_855del
LRG_94:g.8899AAG[3]
NC_000010.10:g.72358622_72358624del
NC_000010.10:g.72358624TCT[3]
NM_001083116.1:c.853_855del
NM_001083116.1:c.853_855delAAG
NM_001083116.3:c.853_855delMANE SELECT

Protein change:

K285del

Links:

dbSNP: rs745902829

NCBI 1000 Genomes Browser:

rs745902829

Molecular consequence:

NM_001083116.3:c.844AAG[3] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_005041.6:c.844AAG[3] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

Recent activity

Clear Turn Off Turn On

Poecilia formosa, whole genome shotgun sequence
Poecilia formosa, whole genome shotgun sequence
gi|553123552|gb|AYCK01003222.1||gnl AYCK01|Poecilia_formosa-5.1.2-28.58

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005010408	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Dec 20, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 11179007, 17873118, 22186995, 25104007, 26184781, 30671214, 32542393, 34938098, 34992599 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005010408

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Dec 20, 2023)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis.

Göransdotter Ericson K, Fadeel B, Nilsson-Ardnor S, Söderhäll C, Samuelsson A, Janka G, Schneider M, Gürgey A, Yalman N, Révész T, Egeler R, Jahnukainen K, Storm-Mathiesen I, Haraldsson A, Poole J, de Saint Basile G, Nordenskjöld M, Henter J.

Am J Hum Genet. 2001 Mar;68(3):590-7. Epub 2001 Feb 6.

PubMed [citation]

PMID:: 11179007
PMCID:: PMC1274472

Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations.

Trizzino A, zur Stadt U, Ueda I, Risma K, Janka G, Ishii E, Beutel K, Sumegi J, Cannella S, Pende D, Mian A, Henter JI, Griffiths G, Santoro A, Filipovich A, Aricò M; Histiocyte Society HLH Study group..

J Med Genet. 2008 Jan;45(1):15-21. Epub 2007 Sep 14.

PubMed [citation]

PMID:: 17873118

See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV005010408.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

The c.853_855delAAG (p.K285del) alteration is located in exon 3 (coding exon 2) of the PRF1 gene. This alteration consists of an in-frame deletion of 3 nucleotides between nucleotide positions c.853 and c.855, resulting in the deletion of 1 residue. Based on data from gnomAD, the c.853_855delAAG (p.K285del) alteration has an overall frequency of 0.006% (16/282750) total alleles studied. The highest observed frequency was 0.048% (5/10366) of Ashkenazi Jewish alleles. This alteration was detected in the homozygous state, and in conjunction with another alteration in PRF1, in multiple individuals with hemophagocytic lymphohistiocytosis (Elsink, 2021; Shi, 2021; Gadoury-Levesque, 2020; Gao, 2019; Tesi, 2015; Chiang, 2014; Chia, 2012; Trizziono, 2008; Göransdotter Ericson, 2001). This amino acid position is not well conserved in available vertebrate species. Functional analysis in KHYG1 shPRF1 cells demonstrated that the p.K285del alteration was detrimental to the cytotoxicity of natural killer (NK) cells (Chia, 2012). This alteration is predicted to be deleterious by in silico analysis (Choi, 2012). Based on the available evidence, this alteration is classified as pathogenic.

#	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

ClinVar

Relating variation to medicine