17-82037444-A-G

Variant names:

• chr17-82037444-A-G
• rs113680823
• NM_016286.4:c.150+6T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_016286.4(DCXR):​c.150+6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,525,646 control chromosomes in the GnomAD database, including 21,224 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.24 (7377 hom., cov: 33)
  • Exomes 𝑓: 0.12 (13847 hom.)
• Consequence: DCXR NM_016286.4 splice_region, intron
• Scores: Splicing: ADA: 0.0009873
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.75

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-82037444-A-G is Benign according to our data. Variant chr17-82037444-A-G is described in ClinVar as [Benign]. Clinvar id is 3057165.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCXR	NM_016286.4	c.150+6T>C		splice_region_variant, intron_variant	Intron 2 of 7	ENST00000306869.7	NP_057370.1
DCXR	NM_001195218.1	c.144+6T>C		splice_region_variant, intron_variant	Intron 2 of 7		NP_001182147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCXR	ENST00000306869.7	c.150+6T>C		splice_region_variant, intron_variant	Intron 2 of 7	1	NM_016286.4	ENSP00000303356.2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35958 AN: 151982 Hom.: 7343 Cov.: 33

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.0629

Gnomad SAS AF: 0.0265

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0897

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.180

GnomAD3 exomes AF: 0.0938 AC: 11384 AN: 121354 Hom.: 978 AF XY: 0.0896 AC XY: 6009 AN XY: 67102

Gnomad AFR exome AF: 0.532

Gnomad AMR exome AF: 0.0650

Gnomad ASJ exome AF: 0.0493

Gnomad EAS exome AF: 0.0636

Gnomad SAS exome AF: 0.0249

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.0884

GnomAD4 exome AF: 0.121 AC: 166580 AN: 1373556 Hom.: 13847 Cov.: 32 AF XY: 0.117 AC XY: 79219 AN XY: 678086

Gnomad4 AFR exome AF: 0.569

Gnomad4 AMR exome AF: 0.0725

Gnomad4 ASJ exome AF: 0.0494

Gnomad4 EAS exome AF: 0.0614

Gnomad4 SAS exome AF: 0.0252

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.237 AC: 36047 AN: 152090 Hom.: 7377 Cov.: 33 AF XY: 0.231 AC XY: 17169 AN XY: 74354

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.0473

Gnomad4 EAS AF: 0.0631

Gnomad4 SAS AF: 0.0261

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.179

Alfa AF: 0.156 Hom.: 725

Bravo AF: 0.248

Asia WGS AF: 0.0790 AC: 275 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DCXR-related disorder Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00099
dbscSNV1_RF	Benign	0.056
SpliceAI score (max)		0.020		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: rs113680823; hg19: chr17-79995320;