8-98123411-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001145860.2(POP1):c.74G>A(p.Gly25Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000931 in 1,614,098 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001145860.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POP1 | NM_001145860.2 | c.74G>A | p.Gly25Asp | missense_variant | Exon 2 of 16 | ENST00000401707.7 | NP_001139332.1 | |
POP1 | NM_001145861.2 | c.74G>A | p.Gly25Asp | missense_variant | Exon 2 of 16 | NP_001139333.1 | ||
POP1 | NM_015029.3 | c.74G>A | p.Gly25Asp | missense_variant | Exon 2 of 16 | NP_055844.2 | ||
POP1 | XM_011516801.3 | c.74G>A | p.Gly25Asp | missense_variant | Exon 2 of 12 | XP_011515103.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POP1 | ENST00000401707.7 | c.74G>A | p.Gly25Asp | missense_variant | Exon 2 of 16 | 2 | NM_001145860.2 | ENSP00000385787.2 | ||
POP1 | ENST00000349693.3 | c.74G>A | p.Gly25Asp | missense_variant | Exon 2 of 16 | 1 | ENSP00000339529.3 | |||
POP1 | ENST00000522319.5 | c.74G>A | p.Gly25Asp | missense_variant | Exon 2 of 5 | 4 | ENSP00000428945.1 |
Frequencies
GnomAD3 genomes AF: 0.000683 AC: 104AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000704 AC: 177AN: 251484Hom.: 0 AF XY: 0.000824 AC XY: 112AN XY: 135920
GnomAD4 exome AF: 0.000957 AC: 1399AN: 1461808Hom.: 4 Cov.: 31 AF XY: 0.000938 AC XY: 682AN XY: 727208
GnomAD4 genome AF: 0.000683 AC: 104AN: 152290Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:2
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 25 of the POP1 protein (p.Gly25Asp). This variant is present in population databases (rs61743394, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with POP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1519057). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -
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Inborn genetic diseases 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. -
POP1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at