Genetic Variant DCXR:c.150+6T>C (chr17-82037444-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_016286.4(DCXR):c.150+6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,525,646 control chromosomes in the GnomAD database, including 21,224 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.24 ( 7377 hom., cov: 33)

Exomes 𝑓: 0.12 ( 13847 hom. )

Consequence

DCXR
NM_016286.4 splice_region, intron

Scores

Splicing: ADA: 0.0009873

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.75

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 17-82037444-A-G is Benign according to our data. Variant chr17-82037444-A-G is described in ClinVar as [Benign]. Clinvar id is 3057165.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCXR	NM_016286.4 link	c.150+6T>C		splice_region_variant, intron_variant	Intron 2 of 7	ENST00000306869.7	NP_057370.1	Q7Z4W1A0A384NY14
DCXR	NM_001195218.1 link	c.144+6T>C		splice_region_variant, intron_variant	Intron 2 of 7		NP_001182147.1	Q7Z4W1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCXR	ENST00000306869.7 link	c.150+6T>C		splice_region_variant, intron_variant	Intron 2 of 7	1	NM_016286.4	ENSP00000303356.2		Q7Z4W1

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

35958

AN:

151982

Hom.:

7343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.561

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.0473

Gnomad EAS

AF:

0.0629

Gnomad SAS

AF:

0.0265

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.0897

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.180

GnomAD3 exomes

AF:

0.0938

AC:

11384

AN:

121354

Hom.:

978

AF XY:

0.0896

AC XY:

6009

AN XY:

67102

show subpopulations

Gnomad AFR exome

AF:

0.532

Gnomad AMR exome

AF:

0.0650

Gnomad ASJ exome

AF:

0.0493

Gnomad EAS exome

AF:

0.0636

Gnomad SAS exome

AF:

0.0249

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.0884

GnomAD4 exome

AF:

0.121

AC:

166580

AN:

1373556

Hom.:

13847

Cov.:

AF XY:

0.117

AC XY:

79219

AN XY:

678086

show subpopulations

Gnomad4 AFR exome

AF:

0.569

Gnomad4 AMR exome

AF:

0.0725

Gnomad4 ASJ exome

AF:

0.0494

Gnomad4 EAS exome

AF:

0.0614

Gnomad4 SAS exome

AF:

0.0252

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.121

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.237

AC:

36047

AN:

152090

Hom.:

7377

Cov.:

AF XY:

0.231

AC XY:

17169

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.562

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.0473

Gnomad4 EAS

AF:

0.0631

Gnomad4 SAS

AF:

0.0261

Gnomad4 FIN

AF:

0.148

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.156

Hom.:

725

Bravo

AF:

0.248

Asia WGS

AF:

0.0790

AC:

275

AN:

3464

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

-0.90

CADD

Benign

5.4

DANN

Benign

0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00099

dbscSNV1_RF

Benign

0.056

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