15-64816593-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_001286496.2(PIF1):c.1847G>A(p.Arg616Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,613,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R616W) has been classified as Uncertain significance.
Frequency
Consequence
NM_001286496.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIF1 | ENST00000559239.2 | c.1847G>A | p.Arg616Gln | missense_variant | Exon 12 of 13 | 1 | NM_001286496.2 | ENSP00000452792.1 | ||
PIF1 | ENST00000333425.10 | c.1847G>A | p.Arg616Gln | missense_variant | Exon 12 of 13 | 1 | ENSP00000328174.6 | |||
PIF1 | ENST00000268043.8 | c.1847G>A | p.Arg616Gln | missense_variant | Exon 12 of 13 | 1 | ENSP00000268043.4 | |||
PIF1 | ENST00000559872.1 | n.*59G>A | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152260Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000601 AC: 15AN: 249430Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135208
GnomAD4 exome AF: 0.0000746 AC: 109AN: 1461230Hom.: 0 Cov.: 32 AF XY: 0.0000839 AC XY: 61AN XY: 726982
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152260Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Submissions by phenotype
not specified Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at