Genetic Variant SDR16C5:p.Glu246Lys (chr8-56305697-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 12/21 in silico tools predict 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21398544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDR16C5	NM_138969.4 link	c.736G>A	p.Glu246Lys	missense_variant	Exon 6 of 7	ENST00000303749.8	NP_620419.2	Q8N3Y7-1B3KT84
SDR16C5	NM_001318049.2 link	c.736G>A	p.Glu246Lys	missense_variant	Exon 6 of 8		NP_001304978.1	Q8N3Y7G3V145B3KT84
SDR16C5	NM_001318050.2 link	c.604G>A	p.Glu202Lys	missense_variant	Exon 5 of 6		NP_001304979.1	Q8N3Y7-2B3KT84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SDR16C5	ENST00000303749.8 link	c.736G>A	p.Glu246Lys	missense_variant	Exon 6 of 7	1	NM_138969.4	ENSP00000307607.3	Q8N3Y7-1
SDR16C5	ENST00000396721.6 link	c.604G>A	p.Glu202Lys	missense_variant	Exon 5 of 6	1		ENSP00000379947.2	Q8N3Y7-2
SDR16C5	ENST00000522671.1 link	c.736G>A	p.Glu246Lys	missense_variant	Exon 6 of 8	2		ENSP00000431010.1	G3V145

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

151092

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00000861

AC:

AN:

232308

Hom.:

AF XY:

0.00000795

AC XY:

AN XY:

125814

show subpopulations

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 SAS 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:

AN:

1441210

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715874

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000265

AC:

AN:

151208

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73764

show subpopulations

Gnomad4 AFR

AF:

0.0000972

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.736G>A (p.E246K) alteration is located in exon 6 (coding exon 5) of the SDR16C5 gene. This alteration results from a G to A substitution at nucleotide position 736, causing the glutamic acid (E) at amino acid position 246 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;T;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.072

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Uncertain

0.13

MutationAssessor

Benign

1.9

.;L;.

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Uncertain

0.30

Sift

Benign

0.11

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.049

B;P;B

Vest4

0.48

MVP

0.84

MPC

0.12

ClinPred

0.90

GERP RS

5.6

Varity_R

0.39

gMVP

0.54

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over