rs77208721
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_022356.4(P3H1):c.611C>A(p.Pro204His) variant causes a missense change. The variant allele was found at a frequency of 0.00129 in 1,613,890 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P204P) has been classified as Likely benign.
Frequency
Consequence
NM_022356.4 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
P3H1 | NM_022356.4 | c.611C>A | p.Pro204His | missense_variant | 2/15 | ENST00000296388.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
P3H1 | ENST00000296388.10 | c.611C>A | p.Pro204His | missense_variant | 2/15 | 1 | NM_022356.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00689 AC: 1048AN: 152010Hom.: 9 Cov.: 32
GnomAD3 exomes AF: 0.00180 AC: 453AN: 251494Hom.: 4 AF XY: 0.00135 AC XY: 183AN XY: 135920
GnomAD4 exome AF: 0.000707 AC: 1034AN: 1461762Hom.: 12 Cov.: 32 AF XY: 0.000580 AC XY: 422AN XY: 727196
GnomAD4 genome ? AF: 0.00690 AC: 1050AN: 152128Hom.: 9 Cov.: 32 AF XY: 0.00664 AC XY: 494AN XY: 74376
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type 8 Benign:3
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 09, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 12, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Osteogenesis Imperfecta, Recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Osteogenesis imperfecta Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Sep 13, 2021 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at