Variant 8-73297221-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_172037.5(RDH10):c.317C>T(p.Pro106Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RDH10
NM_172037.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

Variant links:

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 links:

RDH10 (HGNC:):

RDH10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19235933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RDH10	NM_172037.5 linkuse as main transcript	c.317C>T	p.Pro106Leu	missense_variant	2/6	ENST00000240285.10	NP_742034.1	Q8IZV5A0A024R7X6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RDH10	ENST00000240285.10 linkuse as main transcript	c.317C>T	p.Pro106Leu	missense_variant	2/6	1	NM_172037.5	ENSP00000240285.5	Q8IZV5
RDH10	ENST00000519380 linkuse as main transcript	c.-179C>T		5_prime_UTR_variant	1/5	1		ENSP00000428132.1	E5RK48
RDH10	ENST00000521928.5 linkuse as main transcript	c.-179C>T		5_prime_UTR_variant	2/4	3		ENSP00000429727.1	E5RHJ9
RDH10	ENST00000518870.1 linkuse as main transcript	n.91C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460622

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726754

show subpopulations

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 07, 2024

The c.317C>T (p.P106L) alteration is located in exon 2 (coding exon 2) of the RDH10 gene. This alteration results from a C to T substitution at nucleotide position 317, causing the proline (P) at amino acid position 106 to be replaced by a leucine (L). 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

Benign

0.14

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

Eigen

Benign

0.0042

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

M_CAP

Benign

0.026

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.42

MutationAssessor

Benign

1.1

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.96

REVEL

Benign

0.28

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.024

Polyphen

0.0010

Vest4

0.17

MutPred

0.37

Loss of disorder (P = 0.0839);

MVP

0.38

MPC

1.4

ClinPred

0.80

GERP RS

5.0

Varity_R

0.26

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over