chr8-56305682-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_138969.4(SDR16C5):​c.751G>T​(p.Val251Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000828 in 1,449,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: SDR16C5 NM_138969.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

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>T	p.Val251Phe	missense	Exon 6 of 7	NP_620419.2
	SDR16C5	NM_001318049.2		c.751G>T	p.Val251Phe	missense	Exon 6 of 8	NP_001304978.1	G3V145
	SDR16C5	NM_001318050.2		c.619G>T	p.Val207Phe	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>T	p.Val251Phe	missense	Exon 6 of 7	ENSP00000307607.3	Q8N3Y7-1
	SDR16C5	ENST00000396721.6	TSL:1	c.619G>T	p.Val207Phe	missense	Exon 5 of 6	ENSP00000379947.2	Q8N3Y7-2
	SDR16C5	ENST00000522671.1	TSL:2	c.751G>T	p.Val251Phe	missense	Exon 6 of 8	ENSP00000431010.1	G3V145

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000249 AC: 6 AN: 240702 AF XY: 0.0000231

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000127

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: 0.000172

GnomAD4 exome AF: 0.00000828 AC: 12 AN: 1449432 Hom.: 0 Cov.: 30 AF XY: 0.00000972 AC XY: 7 AN XY: 720338

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

American (AMR) AF: 0.000166 AC: 7 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: 0.00000361 AC: 4 AN: 1108192

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

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	Pathogenic	0.82
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.039
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		2.9
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.017	D
Polyphen		0.82	P
Vest4		0.66
MutPred		0.70		Gain of ubiquitination at K248 (P = 0.1283)
MVP		0.88
MPC		0.23
ClinPred		0.52	D
GERP RS		5.6
Varity_R		0.30
gMVP		0.73
Mutation Taster		=87/13	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: rs754737737; hg19: chr8-57218241;