chr19-55048371-C-T

Variant names:

• chr19-55048371-C-T
• rs777454518
• NM_001145971.2:c.616G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001145971.2(RDH13):​c.616G>A​(p.Ala206Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,872 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: RDH13 NM_001145971.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79
• Publications: 0 publications found

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]

ENSG00000267149 (HGNC:):

GP6-AS1 (HGNC:55305): (GP6 antisense RNA 1)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.973

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145971.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH13	NM_001145971.2	MANE Select	c.616G>A	p.Ala206Thr	missense	Exon 5 of 7	NP_001139443.1	Q8NBN7-1
	RDH13	NM_138412.4		c.403G>A	p.Ala135Thr	missense	Exon 6 of 8	NP_612421.1	Q8NBN7-2
	RDH13	NR_027381.2		n.732G>A		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH13	ENST00000415061.8	TSL:1 MANE Select	c.616G>A	p.Ala206Thr	missense	Exon 5 of 7	ENSP00000391121.2	Q8NBN7-1
	RDH13	ENST00000396247.7	TSL:1	c.403G>A	p.Ala135Thr	missense	Exon 6 of 8	ENSP00000379547.2	Q8NBN7-2
	RDH13	ENST00000610356.4	TSL:1	c.403G>A	p.Ala135Thr	missense	Exon 5 of 7	ENSP00000477732.1	Q8NBN7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461872 Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.73	D
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		5.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-4.0	D
REVEL	Pathogenic	0.89
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.79		Loss of MoRF binding (P = 0.128)
MVP		0.93
MPC		0.39
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.58
gMVP		0.82
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs777454518; hg19: chr19-55559739; COSMIC: COSV52562860; COSMIC: COSV52562860;