12-55721801-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002905.5(RDH5):c.423C>T(p.Ile141Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,613,824 control chromosomes in the GnomAD database, including 41,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2531 hom., cov: 32)

Exomes 𝑓: 0.22 ( 38528 hom. )

Consequence

RDH5
NM_002905.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.74

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 12-55721801-C-T is Benign according to our data. Variant chr12-55721801-C-T is described in ClinVar as [Benign]. Clinvar id is 258857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-55721801-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RDH5	NM_002905.5 link	c.423C>T	p.Ile141Ile	synonymous_variant	Exon 3 of 5	ENST00000257895.10	NP_002896.2	Q92781A0A024RB18
RDH5	NM_001199771.3 link	c.423C>T	p.Ile141Ile	synonymous_variant	Exon 3 of 5		NP_001186700.1	Q92781A0A024RB18
BLOC1S1-RDH5	NR_037658.1 link	n.482C>T		non_coding_transcript_exon_variant	Exon 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RDH5	ENST00000257895.10 link	c.423C>T	p.Ile141Ile	synonymous_variant	Exon 3 of 5	1	NM_002905.5	ENSP00000257895.6		Q92781
ENSG00000258311	ENST00000550412.5 link	c.*95C>T		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000447650.1		F8W036

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24249

AN:

152058

Hom.:

2535

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0404

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.180

GnomAD3 exomes

AF:

0.191

AC:

47634

AN:

250026

Hom.:

5425

AF XY:

0.206

AC XY:

27843

AN XY:

135302

show subpopulations

Gnomad AFR exome

AF:

0.0383

Gnomad AMR exome

AF:

0.0884

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.326

Gnomad FIN exome

AF:

0.158

Gnomad NFE exome

AF:

0.223

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.223

AC:

325747

AN:

1461648

Hom.:

38528

Cov.:

AF XY:

0.227

AC XY:

165306

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0359

Gnomad4 AMR exome

AF:

0.0932

Gnomad4 ASJ exome

AF:

0.222

Gnomad4 EAS exome

AF:

0.0813

Gnomad4 SAS exome

AF:

0.329

Gnomad4 FIN exome

AF:

0.165

Gnomad4 NFE exome

AF:

0.233

Gnomad4 OTH exome

AF:

0.218

GnomAD4 genome

AF:

0.159

AC:

24225

AN:

152176

Hom.:

2531

Cov.:

AF XY:

0.158

AC XY:

11760

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0403

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.108

Gnomad4 SAS

AF:

0.338

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.197

Hom.:

3287

Bravo

AF:

0.148

Asia WGS

AF:

0.224

AC:

779

AN:

3478

EpiCase

AF:

0.225

EpiControl

AF:

0.220

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30747064) -

Pigmentary retinal dystrophy

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.1

DANN

Benign

0.81

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