rs10999426

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001083116.3(PRF1):c.539+82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,573,042 control chromosomes in the GnomAD database, including 69,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4813 hom., cov: 32)

Exomes 𝑓: 0.29 ( 64989 hom. )

Consequence

PRF1
NM_001083116.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.266

Variant links:

Genes affected

PRF1 (HGNC:9360): (perforin 1) This gene encodes a protein with structural similarities to complement component C9 that is important in immunity. This protein forms membrane pores that allow the release of granzymes and subsequent cytolysis of target cells. Whether pore formation occurs in the plasma membrane of target cells or in an endosomal membrane inside target cells is subject to debate. Mutations in this gene are associated with a variety of human disease including diabetes, multiple sclerosis, lymphomas, autoimmune lymphoproliferative syndrome (ALPS), aplastic anemia, and familial hemophagocytic lymphohistiocytosis type 2 (FHL2), a rare and lethal autosomal recessive disorder of early childhood. [provided by RefSeq, Aug 2017]

PRF1 links:

PALD1 (HGNC:23530): (phosphatase domain containing paladin 1) Predicted to enable protein tyrosine phosphatase activity. Predicted to be involved in peptidyl-tyrosine dephosphorylation. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

PALD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-70600282-G-A is Benign according to our data. Variant chr10-70600282-G-A is described in ClinVar as [Benign]. Clinvar id is 1181354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRF1	NM_001083116.3 link	c.539+82C>T		intron_variant	Intron 2 of 2	ENST00000441259.2	NP_001076585.1	P14222
PRF1	NM_005041.6 link	c.539+82C>T		intron_variant	Intron 2 of 2		NP_005032.2	P14222

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRF1	ENST00000441259.2 link	c.539+82C>T		intron_variant	Intron 2 of 2	5	NM_001083116.3	ENSP00000398568.1		P14222

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34058

AN:

151954

Hom.:

4815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0762

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.0237

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.258

GnomAD4 exome

AF:

0.293

AC:

416201

AN:

1420970

Hom.:

64989

AF XY:

0.291

AC XY:

204962

AN XY:

704050

show subpopulations

Gnomad4 AFR exome

AF:

0.0738

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.311

Gnomad4 EAS exome

AF:

0.0205

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.252

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.271

GnomAD4 genome

AF:

0.224

AC:

34055

AN:

152072

Hom.:

4813

Cov.:

AF XY:

0.219

AC XY:

16290

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0761

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.315

Gnomad4 EAS

AF:

0.0239

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.323

Gnomad4 OTH

AF:

0.255

Alfa

AF:

0.264

Hom.:

749

Bravo

AF:

0.218

Asia WGS

AF:

0.107

AC:

372

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over