rs756652599
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_022356.4(P3H1):c.210C>T(p.Ala70=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,591,314 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000076 ( 0 hom. )
Consequence
P3H1
NM_022356.4 synonymous
NM_022356.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.249
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 1-42766762-G-A is Benign according to our data. Variant chr1-42766762-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 468980.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.249 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
P3H1 | NM_022356.4 | c.210C>T | p.Ala70= | synonymous_variant | 1/15 | ENST00000296388.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
P3H1 | ENST00000296388.10 | c.210C>T | p.Ala70= | synonymous_variant | 1/15 | 1 | NM_022356.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000491 AC: 1AN: 203806Hom.: 0 AF XY: 0.00000882 AC XY: 1AN XY: 113362
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GnomAD4 exome AF: 0.00000764 AC: 11AN: 1439102Hom.: 0 Cov.: 32 AF XY: 0.00000979 AC XY: 7AN XY: 714654
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74358
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Osteogenesis imperfecta type 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 20, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at