12-56954973-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003708.5(RDH16):​c.505G>A​(p.Val169Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: RDH16 NM_003708.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -11.1
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.123152345).

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>A	p.Val169Met	missense	Exon 2 of 4	NP_003699.3
	RDH16	NM_001320108.2		c.138-1983G>A		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>A	p.Val169Met	missense	Exon 2 of 4	ENSP00000381206.3	O75452
	RDH16	ENST00000360752.4	TSL:1	n.2226-1983G>A		intron	N/A
	RDH16	ENST00000869325.1		c.637G>A	p.Val213Met	missense	Exon 3 of 5	ENSP00000539384.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000140 AC: 35 AN: 249292 AF XY: 0.000163

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000257

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000157 AC: 229 AN: 1461872 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 117 AN XY: 727236

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

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000177 AC: 197 AN: 1112008

Other (OTH) AF: 0.000215 AC: 13 AN: 60392

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68034

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000207 Hom.: 0

Bravo AF: 0.0000945

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000590 AC: 5

ExAC AF: 0.000215 AC: 26

EpiCase AF: 0.000273

EpiControl AF: 0.000415

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	Benign	0.31
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.0020
DANN	Benign	0.67
DEOGEN2	Benign	0.27	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.1	L
PhyloP100		-11
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.99	N
REVEL	Uncertain	0.31
Sift	Benign	0.038	D
Sift4G	Benign	0.26	T
Polyphen		0.41	B
Vest4		0.30
MVP		0.14
MPC		0.19
ClinPred		0.050	T
GERP RS		-10
Varity_R		0.034
gMVP		0.41
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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; COSMIC: COSV62458364;