10-70597843-TAAAAAA-TAAA

Variant names:

• chr10-70597843-TAAA-T
• rs34914326
• NM_001083116.3:c.*207_*209delTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001083116.3(PRF1):​c.*207_*209delTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 591,566 control chromosomes in the GnomAD database, including 26 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (26 hom., cov: 0)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: PRF1 NM_001083116.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.881

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1764/139096) while in subpopulation AFR AF= 0.0256 (975/38126). AF 95% confidence interval is 0.0242. There are 26 homozygotes in gnomad4. There are 802 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRF1	NM_001083116.3	c.*207_*209delTTT		3_prime_UTR_variant	Exon 3 of 3	ENST00000441259.2	NP_001076585.1
PRF1	NM_005041.6	c.*207_*209delTTT		3_prime_UTR_variant	Exon 3 of 3		NP_005032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRF1	ENST00000441259	c.*207_*209delTTT		3_prime_UTR_variant	Exon 3 of 3	5	NM_001083116.3	ENSP00000398568.1

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1761 AN: 139050 Hom.: 26 Cov.: 0

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00713

Gnomad FIN AF: 0.00134

Gnomad MID AF: 0.0101

Gnomad NFE AF: 0.00735

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.0107 AC: 4836 AN: 452470 Hom.: 0 AF XY: 0.0110 AC XY: 2602 AN XY: 237414

Gnomad4 AFR exome AF: 0.0386

Gnomad4 AMR exome AF: 0.0120

Gnomad4 ASJ exome AF: 0.00323

Gnomad4 EAS exome AF: 0.000580

Gnomad4 SAS exome AF: 0.0167

Gnomad4 FIN exome AF: 0.00366

Gnomad4 NFE exome AF: 0.0105

Gnomad4 OTH exome AF: 0.0122

GnomAD4 genome AF: 0.0127 AC: 1764 AN: 139096 Hom.: 26 Cov.: 0 AF XY: 0.0120 AC XY: 802 AN XY: 67082

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00739

Gnomad4 FIN AF: 0.00134

Gnomad4 NFE AF: 0.00735

Gnomad4 OTH AF: 0.0120

Alfa AF: 0.000867 Hom.: 140

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs34914326; hg19: chr10-72357599;