NM_016286.4:c.127G>C

Variant names:

• chr17-82037473-C-G
• NM_016286.4:c.127G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016286.4(DCXR):​c.127G>C​(p.Asp43His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,380,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: DCXR NM_016286.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40689018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCXR	NM_016286.4	c.127G>C	p.Asp43His	missense_variant	Exon 2 of 8	ENST00000306869.7	NP_057370.1
DCXR	NM_001195218.1	c.121G>C	p.Asp41His	missense_variant	Exon 2 of 8		NP_001182147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCXR	ENST00000306869.7	c.127G>C	p.Asp43His	missense_variant	Exon 2 of 8	1	NM_016286.4	ENSP00000303356.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1380736 Hom.: 0 Cov.: 32 AF XY: 0.00000293 AC XY: 2 AN XY: 681902

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000380

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.69
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.8	D;.
REVEL	Benign	0.16
Sift	Benign	0.076	T;.
Sift4G	Uncertain	0.043	D;.
Polyphen		0.089	B;.
Vest4		0.34
MutPred		0.36		Gain of MoRF binding (P = 0.0554);.;
MVP		0.92
MPC		0.45
ClinPred		0.75	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.63
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79995349;