rs1858740

Positions:

• chr3-38396881-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005108.4(XYLB):​c.1351-191T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,024 control chromosomes in the GnomAD database, including 16,278 homozygotes. 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: 𝑓 0.43 (16278 hom., cov: 31)
• Consequence: XYLB NM_005108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718

Genes affected

XYLB (HGNC:12839): (xylulokinase) The protein encoded by this gene shares 22% sequence identity with Hemophilus influenzae xylulokinase, and even higher identity to other gene products in C.elegans (45%) and yeast (31-35%), which are thought to belong to a family of enzymes that include fucokinase, gluconokinase, glycerokinase and xylulokinase. These proteins play important roles in energy metabolism. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XYLB	NM_005108.4	c.1351-191T>C		intron_variant		ENST00000207870.8	NP_005099.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XYLB	ENST00000207870.8	c.1351-191T>C		intron_variant		1	NM_005108.4	ENSP00000207870	P1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65399 AN: 151906 Hom.: 16279 Cov.: 31

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.462

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.430 AC: 65399 AN: 152024 Hom.: 16278 Cov.: 31 AF XY: 0.428 AC XY: 31808 AN XY: 74292

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.462

Alfa AF: 0.529 Hom.: 10078

Bravo AF: 0.401

Asia WGS AF: 0.395 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.98
DANN	Benign	0.38

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

LitVar

Other links and lift over

dbSNP: rs1858740; hg19: chr3-38438372;