12-56955025-T-G

Position:

• chr12-56955025-T-G

Variant summary

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

The ENST00000398138.5(RDH16):​c.453A>C​(p.Leu151Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RDH16 ENST00000398138.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.454

Genes affected

RDH16 (HGNC:29674): (retinol dehydrogenase 16) Enables NAD-retinol dehydrogenase activity; androstan-3-alpha,17-beta-diol dehydrogenase activity; and androsterone dehydrogenase activity. Involved in steroid metabolic process. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

RDH16 (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
RDH16	NM_003708.5	c.453A>C	p.Leu151Phe	missense_variant	2/4	ENST00000398138.5	NP_003699.3
RDH16	NM_001320108.2	c.138-2035A>C		intron_variant			NP_001307037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RDH16	ENST00000398138.5	c.453A>C	p.Leu151Phe	missense_variant	2/4	1	NM_003708.5	ENSP00000381206.3
RDH16	ENST00000360752.4	n.2226-2035A>C		intron_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Nov 28, 2023

The c.453A>C (p.L151F) alteration is located in exon 2 (coding exon 2) of the RDH16 gene. This alteration results from a A to C substitution at nucleotide position 453, causing the leucine (L) at amino acid position 151 to be replaced by a phenylalanine (F). 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	0.25
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	0.61	D
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.025	D
Polyphen		0.96	P
Vest4		0.58
MutPred		0.63		Gain of methylation at R153 (P = 0.1148);
MVP		0.62
MPC		0.35
ClinPred		0.98	D
GERP RS		-4.7
Varity_R		0.24
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr12-57348809;