rs1554867945
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001083116.3(PRF1):c.879C>T(p.His293=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000186 in 1,614,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
PRF1
NM_001083116.3 synonymous
NM_001083116.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.36
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 10-70598842-G-A is Benign according to our data. Variant chr10-70598842-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 468310.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRF1 | NM_001083116.3 | c.879C>T | p.His293= | synonymous_variant | 3/3 | ENST00000441259.2 | |
PRF1 | NM_005041.6 | c.879C>T | p.His293= | synonymous_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRF1 | ENST00000441259.2 | c.879C>T | p.His293= | synonymous_variant | 3/3 | 5 | NM_001083116.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152262Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461892Hom.: 0 Cov.: 39 AF XY: 0.00000138 AC XY: 1AN XY: 727246
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152262Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74394
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial hemophagocytic lymphohistiocytosis 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | - - |
Computational scores
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CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at