10-70597843-TAA-T

Position:

• chr10-70597843-TAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001083116.3(PRF1):​c.*208_*209del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 570,000 control chromosomes in the GnomAD database, including 352 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (351 hom., cov: 0)
  • Exomes 𝑓: 0.090 (1 hom.)
• Consequence: PRF1 NM_001083116.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.00

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 -10 ACMG points.

• BP6: Variant 10-70597843-TAA-T is Benign according to our data. Variant chr10-70597843-TAA-T is described in ClinVar as [Benign]. Clinvar id is 1287234.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRF1	NM_001083116.3	c.*208_*209del		3_prime_UTR_variant	3/3	ENST00000441259.2
PRF1	NM_005041.6	c.*208_*209del		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRF1	ENST00000441259.2	c.*208_*209del		3_prime_UTR_variant	3/3	5	NM_001083116.3	P1

Frequencies

GnomAD3 genomes AF: 0.0411 AC: 5710 AN: 138904 Hom.: 351 Cov.: 0

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.000919

Gnomad EAS AF: 0.000429

Gnomad SAS AF: 0.0117

Gnomad FIN AF: 0.00661

Gnomad MID AF: 0.00336

Gnomad NFE AF: 0.00168

Gnomad OTH AF: 0.0331

GnomAD4 exome AF: 0.0896 AC: 38606 AN: 431046 Hom.: 1 AF XY: 0.0920 AC XY: 20817 AN XY: 226184

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.0886

Gnomad4 ASJ exome AF: 0.0666

Gnomad4 EAS exome AF: 0.0263

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.0823

Gnomad4 NFE exome AF: 0.0860

Gnomad4 OTH exome AF: 0.0885

GnomAD4 genome AF: 0.0413 AC: 5735 AN: 138954 Hom.: 351 Cov.: 0 AF XY: 0.0404 AC XY: 2709 AN XY: 67008

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0173

Gnomad4 ASJ AF: 0.000919

Gnomad4 EAS AF: 0.000430

Gnomad4 SAS AF: 0.0115

Gnomad4 FIN AF: 0.00661

Gnomad4 NFE AF: 0.00168

Gnomad4 OTH AF: 0.0329

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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)		0.030		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;