17-82037511-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016286.4(DCXR):​c.89C>T​(p.Thr30Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,541,278 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000024 ( 1 hom. )

Consequence

DCXR
NM_016286.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.176
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13103577).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DCXRNM_016286.4 linkc.89C>T p.Thr30Met missense_variant Exon 2 of 8 ENST00000306869.7 NP_057370.1 Q7Z4W1A0A384NY14
DCXRNM_001195218.1 linkc.83C>T p.Thr28Met missense_variant Exon 2 of 8 NP_001182147.1 Q7Z4W1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DCXRENST00000306869.7 linkc.89C>T p.Thr30Met missense_variant Exon 2 of 8 1 NM_016286.4 ENSP00000303356.2 Q7Z4W1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152212
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000573
AC:
8
AN:
139718
Hom.:
1
AF XY:
0.0000776
AC XY:
6
AN XY:
77272
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000350
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000245
AC:
34
AN:
1389066
Hom.:
1
Cov.:
32
AF XY:
0.0000335
AC XY:
23
AN XY:
686670
show subpopulations
Gnomad4 AFR exome
AF:
0.0000326
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000364
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.24e-7
Gnomad4 OTH exome
AF:
0.0000518
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152212
Hom.:
0
Cov.:
34
AF XY:
0.0000538
AC XY:
4
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000584
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000276
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 13, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.89C>T (p.T30M) alteration is located in exon 2 (coding exon 2) of the DCXR gene. This alteration results from a C to T substitution at nucleotide position 89, causing the threonine (T) at amino acid position 30 to be replaced by a methionine (M). 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
0.13
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
17
DANN
Benign
0.90
DEOGEN2
Benign
0.035
T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.71
T;T
M_CAP
Benign
0.054
D
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.41
N;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-0.40
N;.
REVEL
Benign
0.065
Sift
Benign
0.22
T;.
Sift4G
Benign
0.22
T;.
Polyphen
0.0060
B;.
Vest4
0.17
MutPred
0.51
Gain of MoRF binding (P = 0.0732);.;
MVP
0.75
MPC
0.36
ClinPred
0.023
T
GERP RS
0.93
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.1
Varity_R
0.065
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs753772586; hg19: chr17-79995387; API