14-67722644-T-C
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_152443.3(RDH12):āc.2T>Cā(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000000684 in 1,461,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
RDH12
NM_152443.3 start_lost
NM_152443.3 start_lost
Scores
4
6
6
Clinical Significance
Conservation
PhyloP100: 3.85
Genes affected
RDH12 (HGNC:19977): (retinol dehydrogenase 12) The protein encoded by this gene is an NADPH-dependent retinal reductase whose highest activity is toward 9-cis and all-trans-retinol. The encoded enzyme also plays a role in the metabolism of short-chain aldehydes but does not exhibit steroid dehydrogenase activity. Defects in this gene are a cause of Leber congenital amaurosis type 13 and Retinitis Pigmentosa 53. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RDH12 | NM_152443.3 | c.2T>C | p.Met1? | start_lost | 3/9 | ENST00000551171.6 | |
RDH12 | XM_047430965.1 | c.2T>C | p.Met1? | start_lost | 3/9 | ||
GPHN | XM_047430879.1 | c.1313-12551T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RDH12 | ENST00000551171.6 | c.2T>C | p.Met1? | start_lost | 3/9 | 1 | NM_152443.3 | P1 | |
RDH12 | ENST00000267502.3 | c.2T>C | p.Met1? | start_lost | 2/8 | 5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461462Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727064
GnomAD4 exome
AF:
AC:
1
AN:
1461462
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Cov.:
30
AF XY:
AC XY:
1
AN XY:
727064
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Leber congenital amaurosis Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel | Jul 24, 2023 | Clinical significance based on ACMG v2.0 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
B;B
Vest4
MutPred
Gain of catalytic residue at M1 (P = 0.0095);Gain of catalytic residue at M1 (P = 0.0095);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
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
No publications associated with this variant yet.