Variant 19-55047397-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145971.2(RDH13):c.750C>G(p.Ser250Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,459,564 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

RDH13
NM_001145971.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.87

Variant links:

Genes affected

RDH13 (HGNC:19978): (retinol dehydrogenase 13) This gene encodes a mitochondrial short-chain dehydrogenase/reductase, which catalyzes the reduction and oxidation of retinoids. The encoded enzyme may function in retinoic acid production and may also protect the mitochondria against oxidative stress. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

RDH13 links:

ENSG00000267149 (HGNC:):

ENSG00000267149 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RDH13	NM_001145971.2 linkuse as main transcript	c.750C>G	p.Ser250Arg	missense_variant	6/7	ENST00000415061.8	NP_001139443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RDH13	ENST00000415061.8 linkuse as main transcript	c.750C>G	p.Ser250Arg	missense_variant	6/7	1	NM_001145971.2	ENSP00000391121.2		Q8NBN7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244726

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133210

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1459564

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

726002

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:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 26, 2022

The c.750C>G (p.S250R) alteration is located in exon 6 (coding exon 6) of the RDH13 gene. This alteration results from a C to G substitution at nucleotide position 750, causing the serine (S) at amino acid position 250 to be replaced by an arginine (R). 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

Uncertain

0.36

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.018

.;T;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.062

MetaRNN

Uncertain

0.57

D;D;D

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

-0.26

.;N;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.50

.;N;N

REVEL

Uncertain

0.40

Sift

Benign

0.61

.;T;T

Sift4G

Benign

0.62

T;T;T

Polyphen

0.048

.;B;.

Vest4

0.71

MutPred

0.37

.;Loss of glycosylation at S250 (P = 0.0269);.;

MVP

0.72

MPC

0.14

ClinPred

0.10

GERP RS

2.7

Varity_R

0.10

gMVP

0.76

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