3-38346882-C-T

Variant names:

• chr3-38346882-C-T
• rs1159036300
• NM_005108.4:c.14C>T

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.14C>T​(p.Ala5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 1,368,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: XYLB NM_005108.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.216
• 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=0.09460786).

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.14C>T	p.Ala5Val	missense	Exon 1 of 19	NP_005099.2
	XYLB	NM_001349178.2		c.14C>T	p.Ala5Val	missense	Exon 1 of 20	NP_001336107.1
	XYLB	NM_001349180.2		c.14C>T	p.Ala5Val	missense	Exon 1 of 3	NP_001336109.1	C9J0N9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLB	ENST00000207870.8	TSL:1 MANE Select	c.14C>T	p.Ala5Val	missense	Exon 1 of 19	ENSP00000207870.3	O75191-1
	XYLB	ENST00000854437.1		c.14C>T	p.Ala5Val	missense	Exon 1 of 20	ENSP00000524496.1
	XYLB	ENST00000650590.1		c.14C>T	p.Ala5Val	missense	Exon 1 of 18	ENSP00000496840.1	A0A3B3IRM4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000658 AC: 9 AN: 1368072 Hom.: 0 Cov.: 30 AF XY: 0.00000888 AC XY: 6 AN XY: 675840

African (AFR) AF: 0.00 AC: 0 AN: 28052

American (AMR) AF: 0.00 AC: 0 AN: 33132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24010

East Asian (EAS) AF: 0.000161 AC: 5 AN: 31018

South Asian (SAS) AF: 0.00 AC: 0 AN: 75998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5044

European-Non Finnish (NFE) AF: 0.00000374 AC: 4 AN: 1069008

Other (OTH) AF: 0.00 AC: 0 AN: 56628

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.76	N
PhyloP100		-0.22
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.018
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.040	D
Polyphen		0.0090	B
Vest4		0.075
MutPred		0.30		Loss of glycosylation at P6 (P = 0.054)
MVP		0.11
MPC		0.092
ClinPred		0.059	T
GERP RS		-0.66
PromoterAI		0.38	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.14
Mutation Taster		=96/4	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

dbSNP: rs1159036300; hg19: chr3-38388373;