chr8-56305682-C-T

Variant names:

• chr8-56305682-C-T
• rs754737737
• NM_138969.4:c.751G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138969.4(SDR16C5):​c.751G>A​(p.Val251Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000244 in 1,601,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. V251F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: SDR16C5 NM_138969.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3340419).

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.751G>A	p.Val251Ile	missense	Exon 6 of 7	NP_620419.2
	SDR16C5	NM_001318049.2		c.751G>A	p.Val251Ile	missense	Exon 6 of 8	NP_001304978.1	G3V145
	SDR16C5	NM_001318050.2		c.619G>A	p.Val207Ile	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.751G>A	p.Val251Ile	missense	Exon 6 of 7	ENSP00000307607.3	Q8N3Y7-1
	SDR16C5	ENST00000396721.6	TSL:1	c.619G>A	p.Val207Ile	missense	Exon 5 of 6	ENSP00000379947.2	Q8N3Y7-2
	SDR16C5	ENST00000522671.1	TSL:2	c.751G>A	p.Val251Ile	missense	Exon 6 of 8	ENSP00000431010.1	G3V145

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151824 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000726

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000415 AC: 1 AN: 240702 AF XY: 0.00000768

Gnomad AFR exome AF: 0.00

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: 0.00000903

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000241 AC: 35 AN: 1449432 Hom.: 0 Cov.: 30 AF XY: 0.0000278 AC XY: 20 AN XY: 720338

African (AFR) AF: 0.00 AC: 0 AN: 32834

American (AMR) AF: 0.00 AC: 0 AN: 42140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25958

East Asian (EAS) AF: 0.00 AC: 0 AN: 39018

South Asian (SAS) AF: 0.00 AC: 0 AN: 82272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000307 AC: 34 AN: 1108192

Other (OTH) AF: 0.0000167 AC: 1 AN: 59918

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151824 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74140

African (AFR) AF: 0.0000726 AC: 3 AN: 41314

American (AMR) AF: 0.00 AC: 0 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10512

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.0030	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.9
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.89	N
REVEL	Uncertain	0.39
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.020	D
Polyphen		0.24	B
Vest4		0.34
MutPred		0.67		Gain of methylation at K248 (P = 0.103)
MVP		0.84
MPC		0.062
ClinPred		0.38	T
GERP RS		5.6
Varity_R		0.12
gMVP		0.45
Mutation Taster		=97/3	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: rs754737737; hg19: chr8-57218241;