rs115108794
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_022356.4(P3H1):c.1501C>T(p.Arg501Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000413 in 1,614,076 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R501Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_022356.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
P3H1 | NM_022356.4 | c.1501C>T | p.Arg501Trp | missense_variant | 10/15 | ENST00000296388.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
P3H1 | ENST00000296388.10 | c.1501C>T | p.Arg501Trp | missense_variant | 10/15 | 1 | NM_022356.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00185 AC: 281AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000569 AC: 143AN: 251440Hom.: 1 AF XY: 0.000412 AC XY: 56AN XY: 135898
GnomAD4 exome AF: 0.000264 AC: 386AN: 1461816Hom.: 0 Cov.: 32 AF XY: 0.000238 AC XY: 173AN XY: 727220
GnomAD4 genome ? AF: 0.00185 AC: 281AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.00181 AC XY: 135AN XY: 74454
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type 8 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 04, 2023 | - - |
Osteogenesis Imperfecta, Recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
P3H1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 05, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 24, 2020 | This variant is associated with the following publications: (PMID: 26634552) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at