Variant 3-38374501-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005108.4(XYLB):c.887C>T(p.Ala296Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000479 in 1,461,472 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

XYLB
NM_005108.4 missense, splice_region

Scores

Splicing: ADA: 0.9911

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.13

Variant links:

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]

XYLB links:

XYLB (HGNC:):

XYLB links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XYLB	NM_005108.4 linkuse as main transcript	c.887C>T	p.Ala296Val	missense_variant, splice_region_variant	11/19	ENST00000207870.8	NP_005099.2	O75191-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XYLB	ENST00000207870.8 linkuse as main transcript	c.887C>T	p.Ala296Val	missense_variant, splice_region_variant	11/19	1	NM_005108.4	ENSP00000207870.3		O75191-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251382

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461472

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2024

The c.887C>T (p.A296V) alteration is located in exon 11 (coding exon 11) of the XYLB gene. This alteration results from a C to T substitution at nucleotide position 887, causing the alanine (A) at amino acid position 296 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.098

T;.

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Uncertain

-0.075

MutationAssessor

Benign

1.9

M;.

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.8

D;.

REVEL

Uncertain

0.62

Sift

Uncertain

0.023

D;.

Sift4G

Benign

0.16

T;.

Polyphen

0.089

B;.

Vest4

0.65

MutPred

0.44

Gain of catalytic residue at A296 (P = 0.0862);.;

MVP

0.77

MPC

0.098

ClinPred

0.94

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.65

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.86

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over