rs148338728
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_022356.4(P3H1):c.1761C>T(p.His587=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,613,882 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000038 ( 0 hom. )
Consequence
P3H1
NM_022356.4 synonymous
NM_022356.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.222
Genes affected
P3H1 (HGNC:19316): (prolyl 3-hydroxylase 1) This gene encodes an enzyme that is a member of the collagen prolyl hydroxylase family. These enzymes are localized to the endoplasmic reticulum and their activity is required for proper collagen synthesis and assembly. Mutations in this gene are associated with osteogenesis imperfecta type VIII. Three alternatively spliced transcript variants encoding different isoforms have been described. Other variants may exist, but their biological validity has not been determined. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 1-42748277-G-A is Benign according to our data. Variant chr1-42748277-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 468973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.222 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
P3H1 | NM_022356.4 | c.1761C>T | p.His587= | synonymous_variant | 12/15 | ENST00000296388.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
P3H1 | ENST00000296388.10 | c.1761C>T | p.His587= | synonymous_variant | 12/15 | 1 | NM_022356.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000836 AC: 21AN: 251324Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135852
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GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461696Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 727150
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GnomAD4 genome ? AF: 0.000210 AC: 32AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74334
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Osteogenesis imperfecta type 8 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 09, 2018 | 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at