10-70597843-TA-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001083116.3(PRF1):c.*209del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (3658 hom., cov: 0)
  • Exomes 𝑓: 0.42 (57 hom.)
• Consequence: PRF1 NM_001083116.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.60

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]

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 10-70597843-TA-T is Benign according to our data. Variant chr10-70597843-TA-T is described in ClinVar as [Benign]. Clinvar id is 300321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRF1	NM_001083116.3	c.*209del		3_prime_UTR_variant	3/3	ENST00000441259.2
PRF1	NM_005041.6	c.*209del		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRF1	ENST00000441259.2	c.*209del		3_prime_UTR_variant	3/3	5	NM_001083116.3	P1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 32862 AN: 138866 Hom.: 3658 Cov.: 0

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0251

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.198

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.419 AC: 182401 AN: 435844 Hom.: 57 Cov.: 0 AF XY: 0.418 AC XY: 95712 AN XY: 229006

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.397

Gnomad4 ASJ exome AF: 0.439

Gnomad4 EAS exome AF: 0.436

Gnomad4 SAS exome AF: 0.397

Gnomad4 FIN exome AF: 0.434

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.419

GnomAD4 genome AF: 0.237 AC: 32877 AN: 138914 Hom.: 3658 Cov.: 0 AF XY: 0.236 AC XY: 15820 AN XY: 66964

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0256

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.243

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 67% of patients studied by a panel of primary immunodeficiencies. Number of patients: 59. Only high quality variants are reported. -

Familial hemophagocytic lymphohistiocytosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs34914326; hg19: chr10-72357599;