NM_001083116.3(PRF1):c.445G>A (p.Gly149Ser) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 22, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002473073.4

Allele description [Variation Report for NM_001083116.3(PRF1):c.445G>A (p.Gly149Ser)]

NM_001083116.3(PRF1):c.445G>A (p.Gly149Ser)

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.445G>A (p.Gly149Ser)

Other names:

p.Gly149Ser

HGVS:

NC_000010.11:g.70600458C>T
NG_009615.1:g.7318G>A
NM_001083116.3:c.445G>AMANE SELECT
NM_005041.6:c.445G>A
NP_001076585.1:p.Gly149Ser
NP_005032.2:p.Gly149Ser
LRG_94t1:c.445G>A
LRG_94:g.7318G>A
NC_000010.10:g.72360214C>T
NM_001083116.1:c.445G>A

Protein change:

G149S

Links:

dbSNP: rs147462227

NCBI 1000 Genomes Browser:

rs147462227

Molecular consequence:

NM_001083116.3:c.445G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005041.6:c.445G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002770374	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 22, 2024)	germline	clinical testing	Citation Link,
SCV004226836	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 15, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 11756153, 15755897, 19487666, 23073290, 26184781, 32542393, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002770374

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jan 22, 2024)

germline

clinical testing

Citation Link,

SCV004226836

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 15, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

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	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members.

Kogawa K, Lee SM, Villanueva J, Marmer D, Sumegi J, Filipovich AH.

Blood. 2002 Jan 1;99(1):61-6.

PubMed [citation]

PMID:: 11756153

A functional analysis of the putative polymorphisms A91V and N252S and 22 missense perforin mutations associated with familial hemophagocytic lymphohistiocytosis.

Voskoboinik I, Thia MC, Trapani JA.

Blood. 2005 Jun 15;105(12):4700-6. Epub 2005 Mar 8.

PubMed [citation]

PMID:: 15755897

See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV002770374.3

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

Description

Published functional studies demonstrate a damaging effect with reduced expression and absence of cytotoxic activity (PMID: 15755897); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21881043, 21959744, 24916509, 23073290, 17873118, 23592409, 19487666, 16374518, 11756153, 26184781, 16278825, 27577878, 33694335, 31589614, 34308104, 25297583, 32542393, 36440336, 36964991, 37365821, 15755897)

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV004226836.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (7)

Description

PP3, PM3, PS3, PS4_moderate

#	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		1	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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