8-73297221-C-G

Variant names:

• chr8-73297221-C-G
• rs1324680102
• NM_172037.5:c.317C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_172037.5(RDH10):​c.317C>G​(p.Pro106Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P106L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RDH10 NM_172037.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27821088).

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.317C>G	p.Pro106Arg	missense	Exon 2 of 6	NP_742034.1	Q8IZV5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH10	ENST00000240285.10	TSL:1 MANE Select	c.317C>G	p.Pro106Arg	missense	Exon 2 of 6	ENSP00000240285.5	Q8IZV5
	RDH10	ENST00000519380.1	TSL:1	c.-179C>G		5_prime_UTR	Exon 1 of 5	ENSP00000428132.1	E5RK48
	RDH10	ENST00000852525.1		c.317C>G	p.Pro106Arg	missense	Exon 2 of 5	ENSP00000522584.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	0.62	N
PhyloP100		2.0
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.78	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.015	D
Sift4G	Benign	0.072	T
Polyphen		0.75	P
Vest4		0.29
MutPred		0.39		Loss of catalytic residue at P106 (P = 0.1283)
MVP		0.45
MPC		2.2
ClinPred		0.81	D
GERP RS		5.0
PromoterAI		-0.021	Neutral
Varity_R		0.32
gMVP		0.82
Mutation Taster		=172/128	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: rs1324680102; hg19: chr8-74209456;