NM_001083116.3:c.*207_*209delTTT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate 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. Variant has been reported in ClinVar as Likely benign (★).

• 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: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.881
• 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-TAAA-T is Benign according to our data. Variant chr10-70597843-TAAA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3910817.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 Unknown,AR gene

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.*207_*209delTTT		3_prime_UTR	Exon 3 of 3	NP_001076585.1	P14222
	PRF1	NM_005041.6		c.*207_*209delTTT		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.*207_*209delTTT		3_prime_UTR	Exon 3 of 3	ENSP00000398568.1	P14222
	PRF1	ENST00000373209.2	TSL:1	c.*207_*209delTTT		3_prime_UTR	Exon 3 of 3	ENSP00000362305.1	P14222
	PRF1	ENST00000862973.1		c.*207_*209delTTT		3_prime_UTR	Exon 2 of 2	ENSP00000533032.1

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

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

African (AFR) AF: 0.0386 AC: 474 AN: 12274

American (AMR) AF: 0.0120 AC: 220 AN: 18394

Ashkenazi Jewish (ASJ) AF: 0.00323 AC: 44 AN: 13626

East Asian (EAS) AF: 0.000580 AC: 18 AN: 31052

South Asian (SAS) AF: 0.0167 AC: 714 AN: 42832

European-Finnish (FIN) AF: 0.00366 AC: 105 AN: 28726

Middle Eastern (MID) AF: 0.00767 AC: 15 AN: 1956

European-Non Finnish (NFE) AF: 0.0105 AC: 2930 AN: 277732

Other (OTH) AF: 0.0122 AC: 316 AN: 25878

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

African (AFR) AF: 0.0256 AC: 975 AN: 38126

American (AMR) AF: 0.0103 AC: 141 AN: 13656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3268

East Asian (EAS) AF: 0.00 AC: 0 AN: 4650

South Asian (SAS) AF: 0.00739 AC: 32 AN: 4330

European-Finnish (FIN) AF: 0.00134 AC: 11 AN: 8206

Middle Eastern (MID) AF: 0.0109 AC: 3 AN: 274

European-Non Finnish (NFE) AF: 0.00735 AC: 469 AN: 63820

Other (OTH) AF: 0.0120 AC: 23 AN: 1922

Alfa AF: 0.000867 Hom.: 140

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34914326; hg19: chr10-72357599;