Variant chr19-10021673-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000591589.3(RDH8):c.860G>A(p.Arg287His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

RDH8
ENST00000591589.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

RDH8 (HGNC:14423): (retinol dehydrogenase 8) This gene encodes a member of the short-chain dehydrogenase/reductase family. The encoded protein catalyzes the reduction of all-trans-retinal to all-trans-retinol, the first reaction step of the rhodopsin regeneration pathway. This enzymatic reaction is the rate-limiting step in the visual cycle. [provided by RefSeq, Feb 2014]

RDH8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.111252636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RDH8	NM_015725.4 linkuse as main transcript	c.860G>A	p.Arg287His	missense_variant	6/6	ENST00000591589.3	NP_056540.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RDH8	ENST00000591589.3 linkuse as main transcript	c.860G>A	p.Arg287His	missense_variant	6/6	1	NM_015725.4	ENSP00000466058	P1
RDH8	ENST00000651512.1 linkuse as main transcript	c.920G>A	p.Arg307His	missense_variant	6/6			ENSP00000498711
RDH8	ENST00000587782.1 linkuse as main transcript	c.*67G>A		3_prime_UTR_variant	3/3	2		ENSP00000465773

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461778

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

The c.920G>A (p.R307Q) alteration is located in exon 6 (coding exon 6) of the RDH8 gene. This alteration results from a G to A substitution at nucleotide position 920, causing the arginine (R) at amino acid position 307 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.72

M_CAP

Benign

0.029

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.84

MutationTaster

Benign

0.93

N;N

PrimateAI

Benign

0.40

Sift4G

Benign

0.20

Vest4

0.033

MVP

0.66

MPC

0.19

ClinPred

0.61

GERP RS

2.1

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