rs141401389

Variant names:

• chr8-56305697-C-T
• rs141401389
• NM_138969.4:c.736G>A

Variant summary

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

The NM_138969.4(SDR16C5):​c.736G>A​(p.Glu246Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000314 in 1,592,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SDR16C5 NM_138969.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.97
• Publications: 2 publications found

Genes affected

SDR16C5 (HGNC:30311): (short chain dehydrogenase/reductase family 16C member 5) This gene encodes a member of the short-chain alcohol dehydrogenase/reductase superfamily of proteins and is involved in the oxidation of retinol to retinaldehyde. The encoded protein is associated with the endoplasmic reticulum and is predicted to contain three transmembrane helices, suggesting that it is an integral membrane protein. It recognizes all-trans-retinol and all-trans-retinaldehyde as substrates and exhibits a strong preference for NAD(+)/NADH as cofactors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

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=0.21398544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138969.4. 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
	SDR16C5	NM_138969.4	MANE Select	c.736G>A	p.Glu246Lys	missense	Exon 6 of 7	NP_620419.2
	SDR16C5	NM_001318049.2		c.736G>A	p.Glu246Lys	missense	Exon 6 of 8	NP_001304978.1	G3V145
	SDR16C5	NM_001318050.2		c.604G>A	p.Glu202Lys	missense	Exon 5 of 6	NP_001304979.1	Q8N3Y7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDR16C5	ENST00000303749.8	TSL:1 MANE Select	c.736G>A	p.Glu246Lys	missense	Exon 6 of 7	ENSP00000307607.3	Q8N3Y7-1
	SDR16C5	ENST00000396721.6	TSL:1	c.604G>A	p.Glu202Lys	missense	Exon 5 of 6	ENSP00000379947.2	Q8N3Y7-2
	SDR16C5	ENST00000522671.1	TSL:2	c.736G>A	p.Glu246Lys	missense	Exon 6 of 8	ENSP00000431010.1	G3V145

Frequencies

GnomAD3 genomes AF: 0.0000265 AC: 4 AN: 151092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000975

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000861 AC: 2 AN: 232308 AF XY: 0.00000795

Gnomad AFR exome AF: 0.000131

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441210 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 715874

African (AFR) AF: 0.0000309 AC: 1 AN: 32368

American (AMR) AF: 0.00 AC: 0 AN: 40668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25786

East Asian (EAS) AF: 0.00 AC: 0 AN: 38374

South Asian (SAS) AF: 0.00 AC: 0 AN: 80214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105192

Other (OTH) AF: 0.00 AC: 0 AN: 59586

GnomAD4 genome AF: 0.0000265 AC: 4 AN: 151208 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73764

African (AFR) AF: 0.0000972 AC: 4 AN: 41166

American (AMR) AF: 0.00 AC: 0 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67820

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.000136 Hom.: 0

ExAC AF: 0.0000165 AC: 2

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	0.25
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Benign	1.9	L
PhyloP100		4.0
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.30
Sift	Benign	0.11	T
Sift4G	Benign	0.14	T
Polyphen		0.049	B
Vest4		0.48
MVP		0.84
MPC		0.12
ClinPred		0.90	D
GERP RS		5.6
Varity_R		0.39
gMVP		0.54
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs141401389; hg19: chr8-57218256;