8-73322930-C-T

Variant names:

• chr8-73322930-C-T
• NM_172037.5:c.920C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

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-AS1 (HGNC:51658): (RDH10 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172037.5. 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
	RDH10	NM_172037.5	MANE Select	c.920C>T	p.Ala307Val	missense	Exon 6 of 6	NP_742034.1	Q8IZV5
	RDH10-AS1	NR_125388.1		n.382-843G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH10	ENST00000240285.10	TSL:1 MANE Select	c.920C>T	p.Ala307Val	missense	Exon 6 of 6	ENSP00000240285.5	Q8IZV5
	RDH10	ENST00000519380.1	TSL:1	c.425C>T	p.Ala142Val	missense	Exon 5 of 5	ENSP00000428132.1	E5RK48
	RDH10	ENST00000852525.1		c.821C>T	p.Ala274Val	missense	Exon 5 of 5	ENSP00000522584.1

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

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

American (AMR) AF: 0.00 AC: 0 AN: 44718

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111980

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

GnomAD4 genome Cov.: 33

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	0.86
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
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	-0.039	T
MutationAssessor	Benign	0.76	N
PhyloP100		7.7
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.79	N
REVEL	Uncertain	0.39
Sift	Benign	1.0	T
Sift4G	Benign	1.0	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
Mutation Taster		=8/92	disease causing

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

Other links and lift over

hg19: chr8-74235165;