8-73322930-C-T

Position:

• chr8-73322930-C-T

Variant summary

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

The NM_172037.5(RDH10):​c.920C>T​(p.Ala307Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RDH10 NM_172037.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.73

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 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
RDH10	NM_172037.5	c.920C>T	p.Ala307Val	missense_variant	6/6	ENST00000240285.10	NP_742034.1
RDH10-AS1	NR_125388.1	n.382-843G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RDH10	ENST00000240285.10	c.920C>T	p.Ala307Val	missense_variant	6/6	1	NM_172037.5	ENSP00000240285.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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

Aug 21, 2024

The c.920C>T (p.A307V) alteration is located in exon 6 (coding exon 6) of the RDH10 gene. This alteration results from a C to T substitution at nucleotide position 920, causing the alanine (A) at amino acid position 307 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	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Uncertain	-0.039	T
MutationAssessor	Benign	0.76	N;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.79	N;N
REVEL	Uncertain	0.39
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.96	D;.
Vest4		0.73
MutPred		0.41		Gain of MoRF binding (P = 0.546);.;
MVP		0.79
MPC		1.9
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.20
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr8-74235165;