12-56954973-C-G

Variant names:

• chr12-56954973-C-G
• rs200178029
• NM_003708.5:c.505G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003708.5(RDH16):​c.505G>C​(p.Val169Leu) 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. 16/22 in silico tools predict 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. V169M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RDH16 NM_003708.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -11.1
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07716787).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003708.5. 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
	RDH16	NM_003708.5	MANE Select	c.505G>C	p.Val169Leu	missense	Exon 2 of 4	NP_003699.3
	RDH16	NM_001320108.2		c.138-1983G>C		intron	N/A	NP_001307037.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH16	ENST00000398138.5	TSL:1 MANE Select	c.505G>C	p.Val169Leu	missense	Exon 2 of 4	ENSP00000381206.3	O75452
	RDH16	ENST00000360752.4	TSL:1	n.2226-1983G>C		intron	N/A
	RDH16	ENST00000869325.1		c.637G>C	p.Val213Leu	missense	Exon 3 of 5	ENSP00000539384.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.0010
DANN	Benign	0.15
DEOGEN2	Benign	0.19	T
Eigen	Benign	-2.5
Eigen_PC	Benign	-2.6
FATHMM_MKL	Benign	0.0068	N
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.52	N
PhyloP100		-11
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.28
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.26
MutPred		0.52		Loss of MoRF binding (P = 0.0969)
MVP		0.14
MPC		0.098
ClinPred		0.043	T
GERP RS		-10
Varity_R		0.028
gMVP		0.44
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs200178029; hg19: chr12-57348757;