NM_005108.4:c.788T>C

Variant names:

• chr3-38372677-T-C
• NM_005108.4:c.788T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/21 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
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLB	NM_005108.4	MANE Select	c.788T>C	p.Val263Ala	missense	Exon 10 of 19	NP_005099.2
	XYLB	NM_001349178.2		c.788T>C	p.Val263Ala	missense	Exon 10 of 20	NP_001336107.1
	XYLB	NM_001349179.2		c.377T>C	p.Val126Ala	missense	Exon 8 of 17	NP_001336108.1	O75191-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLB	ENST00000207870.8	TSL:1 MANE Select	c.788T>C	p.Val263Ala	missense	Exon 10 of 19	ENSP00000207870.3	O75191-1
	XYLB	ENST00000854437.1		c.788T>C	p.Val263Ala	missense	Exon 10 of 20	ENSP00000524496.1
	XYLB	ENST00000650590.1		c.707T>C	p.Val236Ala	missense	Exon 9 of 18	ENSP00000496840.1	A0A3B3IRM4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.9
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
Mutation Taster		=85/15	polymorphism

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

hg19: chr3-38414168;