10-70597843-T-TAA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001083116.3(PRF1):​c.*208_*209dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: PRF1 NM_001083116.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• 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: Uncertain_significance. The variant received 0 ACMG points.

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_*209dupTT		3_prime_UTR	Exon 3 of 3	NP_001076585.1	P14222
	PRF1	NM_005041.6		c.*208_*209dupTT		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_*209dupTT		3_prime_UTR	Exon 3 of 3	ENSP00000398568.1	P14222
	PRF1	ENST00000373209.2	TSL:1	c.*208_*209dupTT		3_prime_UTR	Exon 3 of 3	ENSP00000362305.1	P14222
	PRF1	ENST00000862973.1		c.*208_*209dupTT		3_prime_UTR	Exon 2 of 2	ENSP00000533032.1

Frequencies

GnomAD3 genomes AF: 0.0000791 AC: 11 AN: 139112 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000184 AC: 84 AN: 457368 Hom.: 0 Cov.: 0 AF XY: 0.000142 AC XY: 34 AN XY: 240004

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

African (AFR) AF: 0.00366 AC: 45 AN: 12282

American (AMR) AF: 0.000108 AC: 2 AN: 18588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13746

East Asian (EAS) AF: 0.0000320 AC: 1 AN: 31204

South Asian (SAS) AF: 0.0000687 AC: 3 AN: 43656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1982

European-Non Finnish (NFE) AF: 0.0000784 AC: 22 AN: 280710

Other (OTH) AF: 0.000421 AC: 11 AN: 26134

⚠️ 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: 0.0000790 AC: 11 AN: 139160 Hom.: 0 Cov.: 0 AF XY: 0.0000447 AC XY: 3 AN XY: 67116

African (AFR) AF: 0.000288 AC: 11 AN: 38140

American (AMR) AF: 0.00 AC: 0 AN: 13662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3270

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 63840

Other (OTH) AF: 0.00 AC: 0 AN: 1922

Alfa AF: 0.00 Hom.: 140

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34914326; hg19: chr10-72357599;