Variant rs104894373 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5

The ENST00000257895.10(RDH5):c.530T>G(p.Val177Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,178 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 Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RDH5
ENST00000257895.10 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.51

Variant links:

Genes affected

RDH5 (HGNC:9940): (retinol dehydrogenase 5) This gene encodes an enzyme belonging to the short-chain dehydrogenases/reductases (SDR) family. This retinol dehydrogenase functions to catalyze the final step in the biosynthesis of 11-cis retinaldehyde, which is the universal chromophore of visual pigments. Mutations in this gene cause autosomal recessive fundus albipunctatus, a rare form of night blindness that is characterized by a delay in the regeneration of cone and rod photopigments. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S1 (biogenesis of lysosomal organelles complex-1, subunit 1) gene. [provided by RefSeq, Dec 2010]

RDH5 links:

BLOC1S1-RDH5 (HGNC:):

BLOC1S1-RDH5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1

In a mutagenesis_site Decreases androsterone dehydrogenase activity. (size 4) in uniprot entity RDH5_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in ENST00000257895.10

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.908

PP5

Variant 12-55721908-T-G is Pathogenic according to our data. Variant chr12-55721908-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 8007.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-55721908-T-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RDH5	NM_002905.5 linkuse as main transcript	c.530T>G	p.Val177Gly	missense_variant	3/5	ENST00000257895.10	NP_002896.2
BLOC1S1-RDH5	NR_037658.1 linkuse as main transcript	n.589T>G		non_coding_transcript_exon_variant	4/6
RDH5	NM_001199771.3 linkuse as main transcript	c.530T>G	p.Val177Gly	missense_variant	3/5		NP_001186700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RDH5	ENST00000257895.10 linkuse as main transcript	c.530T>G	p.Val177Gly	missense_variant	3/5	1	NM_002905.5	ENSP00000257895	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000807

AC:

AN:

247752

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Fundus albipunctatus, autosomal recessive

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2000

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.29

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

D;D;D

Eigen

Benign

0.046

Eigen_PC

Benign

0.030

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.89

D;.;T

M_CAP

Uncertain

0.20

MetaRNN

Pathogenic

0.91

D;D;D

MetaSVM

Uncertain

0.16

MutationAssessor

Benign

0.97

.;L;L

MutationTaster

Benign

1.0

A;A;A

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-5.6

D;D;D

REVEL

Pathogenic

0.74

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.030

D;D;D

Polyphen

0.99

.;D;D

Vest4

0.77

MutPred

0.80

.;Gain of catalytic residue at K179 (P = 0);Gain of catalytic residue at K179 (P = 0);

MVP

0.99

MPC

0.61

ClinPred

0.86

GERP RS

4.2

Varity_R

0.70

gMVP

0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over