rs34279237
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_001083116.3(PRF1):c.376C>T(p.Arg126Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,613,940 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R126R) has been classified as Likely benign.
Frequency
Consequence
NM_001083116.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRF1 | NM_001083116.3 | c.376C>T | p.Arg126Cys | missense_variant | 2/3 | ENST00000441259.2 | |
PRF1 | NM_005041.6 | c.376C>T | p.Arg126Cys | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRF1 | ENST00000441259.2 | c.376C>T | p.Arg126Cys | missense_variant | 2/3 | 5 | NM_001083116.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000719 AC: 18AN: 250346Hom.: 0 AF XY: 0.0000811 AC XY: 11AN XY: 135552
GnomAD4 exome AF: 0.0000458 AC: 67AN: 1461644Hom.: 1 Cov.: 34 AF XY: 0.0000481 AC XY: 35AN XY: 727144
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74458
ClinVar
Submissions by phenotype
Familial hemophagocytic lymphohistiocytosis 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 29, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 126 of the PRF1 protein (p.Arg126Cys). This variant is present in population databases (rs34279237, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PRF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 536224). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at