Genetic Variant SDR16C5:p.Tyr272Cys (chr8-56305618-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_138969.4(SDR16C5):c.815A>G(p.Tyr272Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000486 in 1,439,784 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

SDR16C5
NM_138969.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.10

Publications

0 publications found

Variant links:

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]

SDR16C5 links:

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ACMG classification

Classification was made for transcript

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_138969.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDR16C5	NM_138969.4	MANE Select	c.815A>G	p.Tyr272Cys	missense	Exon 6 of 7	NP_620419.2
SDR16C5	NM_001318049.2		c.815A>G	p.Tyr272Cys	missense	Exon 6 of 8	NP_001304978.1	G3V145
SDR16C5	NM_001318050.2		c.683A>G	p.Tyr228Cys	missense	Exon 5 of 6	NP_001304979.1	Q8N3Y7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDR16C5	ENST00000303749.8	TSL:1 MANE Select	c.815A>G	p.Tyr272Cys	missense	Exon 6 of 7	ENSP00000307607.3	Q8N3Y7-1
SDR16C5	ENST00000396721.6	TSL:1	c.683A>G	p.Tyr228Cys	missense	Exon 5 of 6	ENSP00000379947.2	Q8N3Y7-2
SDR16C5	ENST00000522671.1	TSL:2	c.815A>G	p.Tyr272Cys	missense	Exon 6 of 8	ENSP00000431010.1	G3V145

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000130

AC:

AN:

231100

AF XY:

0.00000800

show subpopulations

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:

0.0000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000486

AC:

AN:

1439784

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

715406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32238

American (AMR)

AF:

0.00

AC:

AN:

38928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25706

East Asian (EAS)

AF:

0.00

AC:

AN:

38798

South Asian (SAS)

AF:

0.00

AC:

AN:

79610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00000633

AC:

AN:

1105860

Other (OTH)

AF:

0.00

AC:

AN:

59606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.28

CADD

Benign

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.31

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.087

MetaRNN

Uncertain

0.46

MetaSVM

Uncertain

0.018

MutationAssessor

Pathogenic

3.6

PhyloP100

4.1

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-7.0

REVEL

Uncertain

0.53

Sift

Benign

0.039

Sift4G

Benign

0.097

Polyphen

0.042

Vest4

0.50

MutPred

0.50

Gain of methylation at K269 (P = 0.0589)

MVP

0.83

MPC

0.29

ClinPred

0.96

GERP RS

4.5

Varity_R

0.32

gMVP

0.70

Mutation Taster

=29/71

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over