rs875989838
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_018192.4(P3H2):c.297delC(p.Gly100AlafsTer104) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000556 in 1,258,488 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000056 ( 0 hom. )
Consequence
P3H2
NM_018192.4 frameshift
NM_018192.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.180
Publications
3 publications found
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-190120434-CG-C is Pathogenic according to our data. Variant chr3-190120434-CG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 225632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_018192.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| P3H2 | TSL:1 MANE Select | c.297delC | p.Gly100AlafsTer104 | frameshift | Exon 1 of 15 | ENSP00000316881.5 | Q8IVL5-1 | ||
| P3H2 | TSL:1 | c.-64+1768delC | intron | N/A | ENSP00000408947.2 | Q8IVL5-2 | |||
| P3H2 | c.297delC | p.Gly100AlafsTer104 | frameshift | Exon 1 of 15 | ENSP00000565874.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000556 AC: 7AN: 1258488Hom.: 0 Cov.: 32 AF XY: 0.00000809 AC XY: 5AN XY: 617744 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
7
AN:
1258488
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
617744
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
25054
American (AMR)
AF:
AC:
0
AN:
19558
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
19170
East Asian (EAS)
AF:
AC:
0
AN:
27090
South Asian (SAS)
AF:
AC:
1
AN:
63526
European-Finnish (FIN)
AF:
AC:
1
AN:
28818
Middle Eastern (MID)
AF:
AC:
0
AN:
3604
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1020350
Other (OTH)
AF:
AC:
0
AN:
51318
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000369849), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.296
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Myopia, high, with cataract and vitreoretinal degeneration (2)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.