Genetic Variant DCXR:p.Ser115Ser (chr17-82036724-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_016286.4(DCXR):c.345G>A(p.Ser115Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,613,272 control chromosomes in the GnomAD database, including 23,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.24 ( 7672 hom., cov: 33)

Exomes 𝑓: 0.12 ( 15601 hom. )

Consequence

DCXR
NM_016286.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.541

Variant links:

Genes affected

DCXR (HGNC:18985): (dicarbonyl and L-xylulose reductase) The protein encoded by this gene acts as a homotetramer to catalyze diacetyl reductase and L-xylulose reductase reactions. The encoded protein may play a role in the uronate cycle of glucose metabolism and in the cellular osmoregulation in the proximal renal tubules. Defects in this gene are a cause of pentosuria. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2010]

DCXR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 17-82036724-C-T is Benign according to our data. Variant chr17-82036724-C-T is described in ClinVar as [Benign]. Clinvar id is 3055361.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.541 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCXR	NM_016286.4 link	c.345G>A	p.Ser115Ser	synonymous_variant	Exon 4 of 8	ENST00000306869.7	NP_057370.1	Q7Z4W1A0A384NY14
DCXR	NM_001195218.1 link	c.339G>A	p.Ser113Ser	synonymous_variant	Exon 4 of 8		NP_001182147.1	Q7Z4W1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCXR	ENST00000306869.7 link	c.345G>A	p.Ser115Ser	synonymous_variant	Exon 4 of 8	1	NM_016286.4	ENSP00000303356.2		Q7Z4W1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36521

AN:

151862

Hom.:

7633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.573

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.0470

Gnomad EAS

AF:

0.0674

Gnomad SAS

AF:

0.0253

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.185

GnomAD3 exomes

AF:

0.128

AC:

32069

AN:

250784

Hom.:

4148

AF XY:

0.117

AC XY:

15823

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.584

Gnomad AMR exome

AF:

0.0664

Gnomad ASJ exome

AF:

0.0510

Gnomad EAS exome

AF:

0.0697

Gnomad SAS exome

AF:

0.0229

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.123

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.123

AC:

179249

AN:

1461292

Hom.:

15601

Cov.:

AF XY:

0.118

AC XY:

85747

AN XY:

726930

show subpopulations

Gnomad4 AFR exome

AF:

0.587

Gnomad4 AMR exome

AF:

0.0718

Gnomad4 ASJ exome

AF:

0.0503

Gnomad4 EAS exome

AF:

0.0646

Gnomad4 SAS exome

AF:

0.0241

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.121

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.241

AC:

36615

AN:

151980

Hom.:

7672

Cov.:

AF XY:

0.235

AC XY:

17488

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.574

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0470

Gnomad4 EAS

AF:

0.0676

Gnomad4 SAS

AF:

0.0249

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.167

Hom.:

1918

Bravo

AF:

0.253

Asia WGS

AF:

0.0830

AC:

289

AN:

3478

EpiCase

AF:

0.104

EpiControl

AF:

0.103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DCXR-related disorder

Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

3.7

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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