chr8-56316058-C-T

Variant names:

• chr8-56316058-C-T
• NM_138969.4:c.290G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_138969.4(SDR16C5):​c.290G>A​(p.Cys97Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SDR16C5 NM_138969.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.85
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984

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.290G>A	p.Cys97Tyr	missense	Exon 2 of 7	NP_620419.2
	SDR16C5	NM_001318049.2		c.290G>A	p.Cys97Tyr	missense	Exon 2 of 8	NP_001304978.1	G3V145
	SDR16C5	NM_001318050.2		c.290G>A	p.Cys97Tyr	missense	Exon 2 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.290G>A	p.Cys97Tyr	missense	Exon 2 of 7	ENSP00000307607.3	Q8N3Y7-1
	SDR16C5	ENST00000396721.6	TSL:1	c.290G>A	p.Cys97Tyr	missense	Exon 2 of 6	ENSP00000379947.2	Q8N3Y7-2
	SDR16C5	ENST00000522671.1	TSL:2	c.290G>A	p.Cys97Tyr	missense	Exon 2 of 8	ENSP00000431010.1	G3V145

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.67	D
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.8
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-8.9	D
REVEL	Pathogenic	0.90
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.84		Gain of methylation at K102 (P = 0.0627)
MVP		0.96
MPC		0.36
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.94
gMVP		0.89
Mutation Taster		=42/58	disease causing

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: chr8-57228617;