chr3-189995416-T-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_018192.4(P3H2):āc.507A>Gā(p.Glu169=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,613,294 control chromosomes in the GnomAD database, including 85,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.30 ( 7170 hom., cov: 32)
Exomes š: 0.32 ( 78185 hom. )
Consequence
P3H2
NM_018192.4 synonymous
NM_018192.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.148
Genes affected
P3H2 (HGNC:19317): (prolyl 3-hydroxylase 2) This gene encodes a member of the prolyl 3-hydroxylase subfamily of 2-oxo-glutarate-dependent dioxygenases. These enzymes play a critical role in collagen chain assembly, stability and cross-linking by catalyzing post-translational 3-hydroxylation of proline residues. Mutations in this gene are associated with nonsyndromic severe myopia with cataract and vitreoretinal degeneration, and downregulation of this gene may play a role in breast cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 3-189995416-T-C is Benign according to our data. Variant chr3-189995416-T-C is described in ClinVar as [Benign]. Clinvar id is 677171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-189995416-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.148 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
P3H2 | NM_018192.4 | c.507A>G | p.Glu169= | synonymous_variant | 2/15 | ENST00000319332.10 | |
P3H2 | NM_001134418.2 | c.-37A>G | 5_prime_UTR_variant | 2/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
P3H2 | ENST00000319332.10 | c.507A>G | p.Glu169= | synonymous_variant | 2/15 | 1 | NM_018192.4 | P1 | |
P3H2 | ENST00000427335.6 | c.-37A>G | 5_prime_UTR_variant | 2/15 | 1 | ||||
P3H2 | ENST00000426003.1 | c.-37A>G | 5_prime_UTR_variant | 2/4 | 4 | ||||
P3H2 | ENST00000444866.5 | c.-37A>G | 5_prime_UTR_variant | 2/4 | 4 |
Frequencies
GnomAD3 genomes AF: 0.299 AC: 45430AN: 151796Hom.: 7160 Cov.: 32
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GnomAD3 exomes AF: 0.335 AC: 84110AN: 250906Hom.: 14856 AF XY: 0.336 AC XY: 45537AN XY: 135600
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GnomAD4 exome AF: 0.323 AC: 472153AN: 1461380Hom.: 78185 Cov.: 38 AF XY: 0.324 AC XY: 235206AN XY: 727000
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GnomAD4 genome AF: 0.299 AC: 45455AN: 151914Hom.: 7170 Cov.: 32 AF XY: 0.305 AC XY: 22641AN XY: 74222
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 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. - |
Myopia, high, with cataract and vitreoretinal degeneration Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at