17-82037482-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016286.4(DCXR):ā€‹c.118A>Gā€‹(p.Thr40Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,535,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00011 ( 0 hom., cov: 34)
Exomes š‘“: 0.00014 ( 0 hom. )

Consequence

DCXR
NM_016286.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.048543125).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DCXRNM_016286.4 linkc.118A>G p.Thr40Ala missense_variant Exon 2 of 8 ENST00000306869.7 NP_057370.1 Q7Z4W1A0A384NY14
DCXRNM_001195218.1 linkc.112A>G p.Thr38Ala 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.118A>G p.Thr40Ala missense_variant Exon 2 of 8 1 NM_016286.4 ENSP00000303356.2 Q7Z4W1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152088
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.000315
AC:
42
AN:
133530
Hom.:
0
AF XY:
0.000475
AC XY:
35
AN XY:
73662
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:
0.00152
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000154
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000145
AC:
200
AN:
1383572
Hom.:
0
Cov.:
32
AF XY:
0.000198
AC XY:
135
AN XY:
683510
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000549
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00138
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000685
Gnomad4 OTH exome
AF:
0.000121
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152198
Hom.:
0
Cov.:
34
AF XY:
0.000148
AC XY:
11
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.0000383
Hom.:
0
Bravo
AF:
0.0000680
ExAC
AF:
0.000171
AC:
18

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 10, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.118A>G (p.T40A) alteration is located in exon 2 (coding exon 2) of the DCXR gene. This alteration results from a A to G substitution at nucleotide position 118, causing the threonine (T) at amino acid position 40 to be replaced by an alanine (A). 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
Benign
-0.35
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
23
DANN
Benign
0.59
DEOGEN2
Benign
0.11
T;T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.55
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Uncertain
0.28
D
MetaRNN
Benign
0.049
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.24
N;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-4.1
D;.
REVEL
Benign
0.080
Sift
Uncertain
0.014
D;.
Sift4G
Uncertain
0.050
T;.
Polyphen
0.10
B;.
Vest4
0.15
MutPred
0.34
Loss of phosphorylation at T40 (P = 0.1225);.;
MVP
0.84
MPC
0.44
ClinPred
0.093
T
GERP RS
2.5
Varity_R
0.72
gMVP
0.71

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: rs748809586; hg19: chr17-79995358; API