rs369342678
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_022356.4(P3H1):c.689C>T(p.Ala230Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,614,014 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. A230A) has been classified as Likely benign.
Frequency
Consequence
NM_022356.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
P3H1 | NM_022356.4 | c.689C>T | p.Ala230Val | missense_variant | 3/15 | ENST00000296388.10 | NP_071751.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
P3H1 | ENST00000296388.10 | c.689C>T | p.Ala230Val | missense_variant | 3/15 | 1 | NM_022356.4 | ENSP00000296388.5 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152158Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251448Hom.: 0 AF XY: 0.0000809 AC XY: 11AN XY: 135888
GnomAD4 exome AF: 0.000104 AC: 152AN: 1461856Hom.: 0 Cov.: 32 AF XY: 0.0000963 AC XY: 70AN XY: 727228
GnomAD4 genome AF: 0.000125 AC: 19AN: 152158Hom.: 1 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74320
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type 8 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 07, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 230 of the P3H1 protein (p.Ala230Val). This variant is present in population databases (rs369342678, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with P3H1-related conditions. ClinVar contains an entry for this variant (Variation ID: 289859). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 31, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at