10-70597843-TAA-T

Variant names:

• chr10-70597843-TAA-T
• rs34914326
• NM_001083116.3:c.*208_*209delTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001083116.3(PRF1):​c.*208_*209delTT 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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083116.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRF1	NM_001083116.3	MANE Select	c.*208_*209delTT		3_prime_UTR	Exon 3 of 3	NP_001076585.1	P14222
	PRF1	NM_005041.6		c.*208_*209delTT		3_prime_UTR	Exon 3 of 3	NP_005032.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRF1	ENST00000441259.2	TSL:5 MANE Select	c.*208_*209delTT		3_prime_UTR	Exon 3 of 3	ENSP00000398568.1	P14222
	PRF1	ENST00000373209.2	TSL:1	c.*208_*209delTT		3_prime_UTR	Exon 3 of 3	ENSP00000362305.1	P14222
	PRF1	ENST00000862973.1		c.*208_*209delTT		3_prime_UTR	Exon 2 of 2	ENSP00000533032.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.176 AC: 2094 AN: 11918

American (AMR) AF: 0.0886 AC: 1531 AN: 17278

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 868 AN: 13030

East Asian (EAS) AF: 0.0263 AC: 769 AN: 29274

South Asian (SAS) AF: 0.146 AC: 5974 AN: 40896

European-Finnish (FIN) AF: 0.0823 AC: 2234 AN: 27142

Middle Eastern (MID) AF: 0.0850 AC: 160 AN: 1882

European-Non Finnish (NFE) AF: 0.0860 AC: 22786 AN: 264882

Other (OTH) AF: 0.0885 AC: 2190 AN: 24744

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.137 AC: 5219 AN: 38098

American (AMR) AF: 0.0173 AC: 236 AN: 13642

Ashkenazi Jewish (ASJ) AF: 0.000919 AC: 3 AN: 3266

East Asian (EAS) AF: 0.000430 AC: 2 AN: 4646

South Asian (SAS) AF: 0.0115 AC: 50 AN: 4332

European-Finnish (FIN) AF: 0.00661 AC: 54 AN: 8174

Middle Eastern (MID) AF: 0.00365 AC: 1 AN: 274

European-Non Finnish (NFE) AF: 0.00168 AC: 107 AN: 63762

Other (OTH) AF: 0.0329 AC: 63 AN: 1916

Alfa AF: 0.0000963 Hom.: 140

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34914326; hg19: chr10-72357599;