3-38372677-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005108.4(XYLB):c.788T>C(p.Val263Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: XYLB NM_005108.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13211933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XYLB	NM_005108.4	c.788T>C	p.Val263Ala	missense_variant	10/19	ENST00000207870.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XYLB	ENST00000207870.8	c.788T>C	p.Val263Ala	missense_variant	10/19	1	NM_005108.4	P1
XYLB	ENST00000650590.1	c.707T>C	p.Val236Ala	missense_variant	9/18
XYLB	ENST00000649234.1	c.788T>C	p.Val263Ala	missense_variant, NMD_transcript_variant	10/20
XYLB	ENST00000424034.5	c.*451T>C		3_prime_UTR_variant, NMD_transcript_variant	8/17	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2023

The c.788T>C (p.V263A) alteration is located in exon 10 (coding exon 10) of the XYLB gene. This alteration results from a T to C substitution at nucleotide position 788, causing the valine (V) at amino acid position 263 to be replaced by an alanine (A). 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	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	19
Dann	Benign	0.96
DEOGEN2	Benign	0.066	T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.084
Sift	Benign	0.036	D;.
Sift4G	Benign	0.093	T;.
Polyphen		0.090	B;.
Vest4		0.19
MutPred		0.66		Loss of stability (P = 0.0103);.;
MVP		0.18
MPC		0.12
ClinPred		0.21	T
GERP RS		3.0
Varity_R		0.19
gMVP		0.48

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: chr3-38414168;