19-10021323-T-G

Variant names:

• chr19-10021323-T-G
• rs1644731
• NM_015725.4:c.605T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015725.4(RDH8):​c.605T>G​(p.Met202Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: RDH8 NM_015725.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035602123).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015725.4. 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
	RDH8	NM_015725.4	MANE Select	c.605T>G	p.Met202Arg	missense	Exon 5 of 6	NP_056540.3	Q9NYR8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH8	ENST00000591589.3	TSL:1 MANE Select	c.605T>G	p.Met202Arg	missense	Exon 5 of 6	ENSP00000466058.2	Q9NYR8
	RDH8	ENST00000651512.1		c.665T>G	p.Met222Arg	missense	Exon 5 of 6	ENSP00000498711.1	K7ELF7
	RDH8	ENST00000587782.1	TSL:2	c.49T>G	p.Trp17Gly	missense	Exon 2 of 3	ENSP00000465773.1	K7EKT5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.34
DANN	Benign	0.59
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.089	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.66	T
PhyloP100		-0.46
PrimateAI	Benign	0.27	T
Sift4G	Benign	0.55	T
Vest4		0.076
MVP		0.26
MPC		0.23
ClinPred		0.031	T
GERP RS		-2.0
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1644731; hg19: chr19-10131999;