Variant 17-82036061-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_016286.4(DCXR):c.634G>A(p.Val212Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,613,212 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 2 hom. )

Consequence

DCXR
NM_016286.4 missense, splice_region

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.25

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:

DCXR (HGNC:):

DCXR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009116322).

BP6

Variant 17-82036061-C-T is Benign according to our data. Variant chr17-82036061-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3040332.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCXR	NM_016286.4 linkuse as main transcript	c.634G>A	p.Val212Ile	missense_variant, splice_region_variant	8/8	ENST00000306869.7	NP_057370.1	Q7Z4W1A0A384NY14
DCXR	NM_001195218.1 linkuse as main transcript	c.628G>A	p.Val210Ile	missense_variant, splice_region_variant	8/8		NP_001182147.1	Q7Z4W1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCXR	ENST00000306869.7 linkuse as main transcript	c.634G>A	p.Val212Ile	missense_variant, splice_region_variant	8/8	1	NM_016286.4	ENSP00000303356.2		Q7Z4W1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000252

AC:

AN:

250300

Hom.:

AF XY:

0.000206

AC XY:

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00267

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000116

AC:

169

AN:

1460884

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00116

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.000236

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00366

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000215

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000297

AC:

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DCXR-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 15, 2022

This variant is classified as likely 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

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.049

T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.0091

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.91

N;.

REVEL

Benign

0.054

Sift

Benign

0.11

T;.

Sift4G

Benign

0.18

T;.

Polyphen

0.14

B;.

Vest4

0.22

MVP

0.57

MPC

0.35

ClinPred

0.019

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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