Genetic Variant NM_002905.5:c.62G>C (chr12-55721246-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002905.5(RDH5):c.62G>C(p.Arg21Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R21Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RDH5
NM_002905.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.200

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:

ENSG00000258311 (HGNC:):

ENSG00000258311 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3334248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RDH5	NM_002905.5 link	c.62G>C	p.Arg21Pro	missense_variant	Exon 2 of 5	ENST00000257895.10	NP_002896.2	Q92781A0A024RB18
RDH5	NM_001199771.3 link	c.62G>C	p.Arg21Pro	missense_variant	Exon 2 of 5		NP_001186700.1	Q92781A0A024RB18
BLOC1S1-RDH5	NR_037658.1 link	n.370-443G>C		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RDH5	ENST00000257895.10 link	c.62G>C	p.Arg21Pro	missense_variant	Exon 2 of 5	1	NM_002905.5	ENSP00000257895.6		Q92781
ENSG00000258311	ENST00000550412.5 link	c.352-443G>C		intron_variant	Intron 3 of 3	2		ENSP00000447650.1		F8W036

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.77

D;D

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.71

.;T

M_CAP

Benign

0.065

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.85

L;L

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.051

T;T

Polyphen

0.91

P;P

Vest4

0.26

MutPred

0.56

Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);

MVP

0.76

MPC

0.59

ClinPred

0.91

GERP RS

0.73

Varity_R

0.54

gMVP

0.67

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over