3-38403441-G-T

Variant names:

• chr3-38403441-G-T
• rs1002676
• NM_005108.4:c.1533+2456G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005108.4(XYLB):​c.1533+2456G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,072 control chromosomes in the GnomAD database, including 15,767 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 0.42 (15767 hom., cov: 32)
• Consequence: XYLB NM_005108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005108.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLB	NM_005108.4	MANE Select	c.1533+2456G>T		intron	N/A	NP_005099.2
	XYLB	NM_001349178.2		c.1533+2456G>T		intron	N/A	NP_001336107.1
	XYLB	NM_001349179.2		c.1122+2456G>T		intron	N/A	NP_001336108.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLB	ENST00000207870.8	TSL:1 MANE Select	c.1533+2456G>T		intron	N/A	ENSP00000207870.3
	XYLB	ENST00000650590.1		c.1452+2456G>T		intron	N/A	ENSP00000496840.1
	XYLB	ENST00000424034.5	TSL:2	n.*1196+2456G>T		intron	N/A	ENSP00000398845.1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64173 AN: 151952 Hom.: 15769 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.422 AC: 64174 AN: 152072 Hom.: 15767 Cov.: 32 AF XY: 0.420 AC XY: 31182 AN XY: 74318

African (AFR) AF: 0.179 AC: 7431 AN: 41492

American (AMR) AF: 0.384 AC: 5859 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1691 AN: 3472

East Asian (EAS) AF: 0.270 AC: 1395 AN: 5170

South Asian (SAS) AF: 0.506 AC: 2436 AN: 4812

European-Finnish (FIN) AF: 0.525 AC: 5542 AN: 10550

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38320 AN: 67988

Other (OTH) AF: 0.444 AC: 936 AN: 2110

Alfa AF: 0.472 Hom.: 7947

Bravo AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1002676; hg19: chr3-38444932;