Genetic Variant DCXR:c.52+1G>A (chr17-82037630-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016286.4(DCXR):c.52+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,584,522 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

DCXR
NM_016286.4 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Uncertain significance criteria provided, single submitter U:1O:1

Conservation

PhyloP100: 3.49

Publications

3 publications found

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-DT (HGNC:54083): (DCXR divergent transcript)

DCXR-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCXR	NM_016286.4 link	c.52+1G>A		splice_donor_variant, intron_variant	Intron 1 of 7	ENST00000306869.7	NP_057370.1	Q7Z4W1A0A384NY14
DCXR	NM_001195218.1 link	c.52+1G>A		splice_donor_variant, intron_variant	Intron 1 of 7		NP_001182147.1	Q7Z4W1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCXR	ENST00000306869.7 link	c.52+1G>A		splice_donor_variant, intron_variant	Intron 1 of 7	1	NM_016286.4	ENSP00000303356.2		Q7Z4W1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00518

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

GnomAD2 exomes

AF:

0.000322

AC:

AN:

198492

AF XY:

0.000343

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00519

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000148

Gnomad OTH exome

AF:

0.000778

GnomAD4 exome

AF:

0.000201

AC:

288

AN:

1432286

Hom.:

Cov.:

AF XY:

0.000200

AC XY:

142

AN XY:

711754

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33124

American (AMR)

AF:

0.00

AC:

AN:

42978

Ashkenazi Jewish (ASJ)

AF:

0.00485

AC:

125

AN:

25748

East Asian (EAS)

AF:

0.00

AC:

AN:

38980

South Asian (SAS)

AF:

0.00

AC:

AN:

83890

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.000130

AC:

144

AN:

1105124

Other (OTH)

AF:

0.000319

AC:

AN:

59616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000138

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00518

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000863

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000497

AC:

ExAC

AF:

0.000180

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Essential pentosuria

Uncertain:1Other:1

Nov 08, 2011

OMIM

Significance:Affects

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Sep 23, 2022

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.24

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.89

PhyloP100

3.5

GERP RS

3.9

PromoterAI

0.082

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Mutation Taster

=42/58

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.95

SpliceAI score (max)

0.98

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.63

Position offset: -16

DS_DL_spliceai

0.98

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over