17-82036904-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016286.4(DCXR):​c.260C>T​(p.Ala87Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,692 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DCXR
NM_016286.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.43
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DCXRNM_016286.4 linkc.260C>T p.Ala87Val missense_variant Exon 3 of 8 ENST00000306869.7 NP_057370.1 Q7Z4W1A0A384NY14
DCXRNM_001195218.1 linkc.254C>T p.Ala85Val missense_variant Exon 3 of 8 NP_001182147.1 Q7Z4W1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DCXRENST00000306869.7 linkc.260C>T p.Ala87Val missense_variant Exon 3 of 8 1 NM_016286.4 ENSP00000303356.2 Q7Z4W1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000803
AC:
2
AN:
248934
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135210
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000892
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460692
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
726652
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000825
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.260C>T (p.A87V) alteration is located in exon 3 (coding exon 3) of the DCXR gene. This alteration results from a C to T substitution at nucleotide position 260, causing the alanine (A) at amino acid position 87 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Uncertain
0.057
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
22
DANN
Benign
0.95
DEOGEN2
Benign
0.11
.;T;T;T
Eigen
Benign
-0.043
Eigen_PC
Benign
-0.014
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.88
D;T;T;T
M_CAP
Benign
0.065
D
MetaRNN
Uncertain
0.45
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.015
.;N;.;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.0
.;D;.;.
REVEL
Benign
0.19
Sift
Benign
0.049
.;D;.;.
Sift4G
Benign
0.12
T;D;.;D
Polyphen
0.69
.;P;.;.
Vest4
0.35
MutPred
0.49
.;Gain of sheet (P = 0.0477);.;.;
MVP
0.96
MPC
0.44
ClinPred
0.46
T
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.30
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
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.

Other links and lift over

dbSNP: rs772531200; hg19: chr17-79994780; API