12-56952100-T-C

Variant names:

• chr12-56952100-T-C
• NM_003708.5:c.883A>G

Variant summary

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

The NM_003708.5(RDH16):​c.883A>G​(p.Ser295Gly) 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 NM_003708.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.883A>G	p.Ser295Gly	missense	Exon 4 of 4	NP_003699.3
	RDH16	NM_001320108.2		c.448A>G	p.Ser150Gly	missense	Exon 3 of 3	NP_001307037.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH16	ENST00000398138.5	TSL:1 MANE Select	c.883A>G	p.Ser295Gly	missense	Exon 4 of 4	ENSP00000381206.3	O75452
	RDH16	ENST00000360752.4	TSL:1	n.2536A>G		non_coding_transcript_exon	Exon 3 of 3
	RDH16	ENST00000869325.1		c.1015A>G	p.Ser339Gly	missense	Exon 5 of 5	ENSP00000539384.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.29
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Pathogenic	0.99	D
MutationAssessor	Pathogenic	3.7	H
PhyloP100		1.9
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.7	D
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.94	P
Vest4		0.51
MutPred		0.48		Loss of stability (P = 0.0755)
MVP		0.77
MPC		0.46
ClinPred		0.98	D
GERP RS		3.7
Varity_R		0.25
gMVP		0.39
Mutation Taster		=70/30	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

hg19: chr12-57345884;