17-82036434-C-T

Variant names:

• chr17-82036434-C-T
• rs775400332
• NM_016286.4:c.463G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016286.4(DCXR):​c.463G>A​(p.Ala155Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCXR NM_016286.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.11

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCXR	NM_016286.4	c.463G>A	p.Ala155Thr	missense_variant	Exon 6 of 8	ENST00000306869.7	NP_057370.1
DCXR	NM_001195218.1	c.457G>A	p.Ala153Thr	missense_variant	Exon 6 of 8		NP_001182147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCXR	ENST00000306869.7	c.463G>A	p.Ala155Thr	missense_variant	Exon 6 of 8	1	NM_016286.4	ENSP00000303356.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.40
CADD	Uncertain	25
DANN	Benign	0.93
DEOGEN2	Benign	0.13	.;T;T;D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.90	D;D;D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Pathogenic	3.7	.;H;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.6	.;D;.;.
REVEL	Uncertain	0.47
Sift	Uncertain	0.0020	.;D;.;.
Sift4G	Uncertain	0.0020	D;D;.;D
Polyphen		0.99	.;D;.;.
Vest4		0.97
MutPred		0.79		.;Loss of ubiquitination at K153 (P = 0.0579);.;.;
MVP		0.96
MPC		1.1
ClinPred		0.99	D
GERP RS		3.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.88
gMVP		0.95

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

Other links and lift over

dbSNP: rs775400332; hg19: chr17-79994310;