8-56316016-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138969.4(SDR16C5):c.332A>G(p.Gln111Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000035 in 1,602,178 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

SDR16C5
NM_138969.4 missense, splice_region

Scores

Splicing: ADA: 0.9983

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDR16C5	NM_138969.4 link	c.332A>G	p.Gln111Arg	missense_variant, splice_region_variant	Exon 2 of 7	ENST00000303749.8	NP_620419.2	Q8N3Y7-1B3KT84
SDR16C5	NM_001318049.2 link	c.332A>G	p.Gln111Arg	missense_variant, splice_region_variant	Exon 2 of 8		NP_001304978.1	Q8N3Y7G3V145B3KT84
SDR16C5	NM_001318050.2 link	c.332A>G	p.Gln111Arg	missense_variant, splice_region_variant	Exon 2 of 6		NP_001304979.1	Q8N3Y7-2B3KT84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SDR16C5	ENST00000303749.8 link	c.332A>G	p.Gln111Arg	missense_variant, splice_region_variant	Exon 2 of 7	1	NM_138969.4	ENSP00000307607.3	Q8N3Y7-1
SDR16C5	ENST00000396721.6 link	c.332A>G	p.Gln111Arg	missense_variant, splice_region_variant	Exon 2 of 6	1		ENSP00000379947.2	Q8N3Y7-2
SDR16C5	ENST00000522671.1 link	c.332A>G	p.Gln111Arg	missense_variant, splice_region_variant	Exon 2 of 8	2		ENSP00000431010.1	G3V145

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

249194

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134612

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000359

AC:

AN:

1450000

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

721648

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000472

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.332A>G (p.Q111R) alteration is located in exon 2 (coding exon 1) of the SDR16C5 gene. This alteration results from a A to G substitution at nucleotide position 332, causing the glutamine (Q) at amino acid position 111 to be replaced by an arginine (R). 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

0.087

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

.;T;D

Eigen

Benign

-0.011

Eigen_PC

Benign

0.099

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.33

T;T;T

M_CAP

Benign

0.078

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

-0.20

N;N;.

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Uncertain

0.43

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.15

B;D;P

Vest4

0.58

MutPred

0.41

Gain of MoRF binding (P = 0.0235);Gain of MoRF binding (P = 0.0235);Gain of MoRF binding (P = 0.0235);

MVP

0.84

MPC

0.21

ClinPred

0.44

GERP RS

3.9

Varity_R

0.25

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.97

SpliceAI score (max)

0.17

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