Variant 17-82036238-TG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP5BS2

The NM_016286.4(DCXR):c.583delC(p.His195ThrfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000534 in 1,613,508 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Pathogenic,Affects (no stars).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 6 hom. )

Consequence

DCXR
NM_016286.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic; Affects no assertion criteria provided P:1O:1

Conservation

PhyloP100: 1.97

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 Likely_benign. Variant got -3 ACMG points.

PP5

Variant 17-82036238-TG-T is Pathogenic according to our data. Variant chr17-82036238-TG-T is described in ClinVar as [Pathogenic, Affects]. Clinvar id is 101054.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCXR	NM_016286.4 link	c.583delC	p.His195ThrfsTer7	frameshift_variant	Exon 7 of 8	ENST00000306869.7	NP_057370.1	Q7Z4W1A0A384NY14
DCXR	NM_001195218.1 link	c.577delC	p.His193ThrfsTer7	frameshift_variant	Exon 7 of 8		NP_001182147.1	Q7Z4W1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCXR	ENST00000306869.7 link	c.583delC	p.His195ThrfsTer7	frameshift_variant	Exon 7 of 8	1	NM_016286.4	ENSP00000303356.2		Q7Z4W1

Frequencies

GnomAD3 genomes

AF:

0.000638

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00101

AC:

252

AN:

250564

Hom.:

AF XY:

0.00108

AC XY:

146

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.0214

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.000523

AC:

764

AN:

1461386

Hom.:

Cov.:

AF XY:

0.000536

AC XY:

390

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0208

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000971

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.000638

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.000525

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0239

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.00346

Hom.:

Bravo

AF:

0.000661

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Pathogenic; Affects

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DCXR-related disorder

Pathogenic:1

Mar 23, 2024

PreventionGenetics, part of Exact Sciences

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

The DCXR c.583delC variant is predicted to result in a frameshift and premature protein termination (p.His195Thrfs*7). This variant has been reported in the homozygous or compound heterozygous state in individuals with biochemically confirmed pentosuria (Pierce et al. 2011. PubMed ID: 22042873). This variant is reported in 2.1% of alleles in individuals of Ashkenazi Jewish descent in gnomAD, which is consistent with high reported frequency of this trait in individuals of Ashkenazi Jewish descent (Pierce et al. 2011. PubMed ID: 22042873). This variant is interpreted as pathogenic. Of note, pentosuria is characterized by increased urinary excretion of L-xyluloseconsidered and is considered a benign trait (OMIM: #260800; Pierce et al. 2011. PubMed ID: 22042873). -

Essential pentosuria

Other:1

Nov 08, 2011

OMIM

Significance: Affects

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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