GeneBe

rs9821880

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000427335.6(P3H2):​c.-37A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

P3H2
ENST00000427335.6 5_prime_UTR_premature_start_codon_gain

Scores

2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.148

Publications

17 publications found
Variant links:
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]
P3H2 Gene-Disease associations (from GenCC):
  • myopia, high, with cataract and vitreoretinal degeneration
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.24901453).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000427335.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
P3H2
NM_018192.4
MANE Select
c.507A>Tp.Glu169Asp
missense
Exon 2 of 15NP_060662.2
P3H2
NM_001134418.2
c.-37A>T
5_prime_UTR_premature_start_codon_gain
Exon 2 of 15NP_001127890.1
P3H2
NM_001134418.2
c.-37A>T
5_prime_UTR
Exon 2 of 15NP_001127890.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
P3H2
ENST00000427335.6
TSL:1
c.-37A>T
5_prime_UTR_premature_start_codon_gain
Exon 2 of 15ENSP00000408947.2
P3H2
ENST00000319332.10
TSL:1 MANE Select
c.507A>Tp.Glu169Asp
missense
Exon 2 of 15ENSP00000316881.5
P3H2
ENST00000427335.6
TSL:1
c.-37A>T
5_prime_UTR
Exon 2 of 15ENSP00000408947.2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
38
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.064
T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.18
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.0082
T
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M
PhyloP100
0.15
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.86
N
REVEL
Benign
0.095
Sift
Benign
0.13
T
Sift4G
Benign
0.22
T
Polyphen
0.0010
B
Vest4
0.15
MutPred
0.27
Loss of ubiquitination at K166 (P = 0.0896)
MVP
0.37
MPC
0.054
ClinPred
0.67
D
GERP RS
4.1
Varity_R
0.055
gMVP
0.25
Mutation Taster
=92/8
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs9821880; hg19: chr3-189713205; API