8-73322941-A-G

Position:

• chr8-73322941-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_172037.5(RDH10):​c.931A>G​(p.Met311Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 33)
• Consequence: RDH10 NM_172037.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.11

Genes affected

RDH10 (HGNC:19975): (retinol dehydrogenase 10) This gene encodes a retinol dehydrogenase, which converts all-trans-retinol to all-trans-retinal, with preference for NADP as a cofactor. Studies in mice suggest that this protein is essential for synthesis of embryonic retinoic acid and is required for limb, craniofacial, and organ development. [provided by RefSeq, Dec 2011]

RDH10 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34149018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RDH10	NM_172037.5	c.931A>G	p.Met311Val	missense_variant	6/6	ENST00000240285.10	NP_742034.1
RDH10-AS1	NR_125388.1	n.382-854T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RDH10	ENST00000240285.10	c.931A>G	p.Met311Val	missense_variant	6/6	1	NM_172037.5	ENSP00000240285.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.931A>G (p.M311V) alteration is located in exon 6 (coding exon 6) of the RDH10 gene. This alteration results from a A to G substitution at nucleotide position 931, causing the methionine (M) at amino acid position 311 to be replaced by a valine (V). 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	0.35
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.31	T;.
Eigen	Benign	-0.067
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.50	N;N
REVEL	Benign	0.15
Sift	Benign	0.26	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.099	B;.
Vest4		0.56
MutPred		0.40		Loss of helix (P = 0.1706);.;
MVP		0.57
MPC		1.4
ClinPred		0.77	D
GERP RS		4.4
Varity_R		0.17
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-74235176;