chr3-38375196-C-G

Position:

• chr3-38375196-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005108.4(XYLB):​c.941C>G​(p.Pro314Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: XYLB NM_005108.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.56

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XYLB	NM_005108.4	c.941C>G	p.Pro314Arg	missense_variant	12/19	ENST00000207870.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XYLB	ENST00000207870.8	c.941C>G	p.Pro314Arg	missense_variant	12/19	1	NM_005108.4	P1
XYLB	ENST00000650590.1	c.860C>G	p.Pro287Arg	missense_variant	11/18
XYLB	ENST00000424034.5	c.*604C>G		3_prime_UTR_variant, NMD_transcript_variant	10/17	2
XYLB	ENST00000649234.1	c.*176C>G		3_prime_UTR_variant, NMD_transcript_variant	13/20

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Apr 09, 2024

The c.941C>G (p.P314R) alteration is located in exon 12 (coding exon 12) of the XYLB gene. This alteration results from a C to G substitution at nucleotide position 941, causing the proline (P) at amino acid position 314 to be replaced by an arginine (R). 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	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.7	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-6.0	D;.
REVEL	Uncertain	0.45
Sift	Uncertain	0.0080	D;.
Sift4G	Benign	0.16	T;.
Polyphen		0.98	D;.
Vest4		0.89
MutPred		0.39		Loss of catalytic residue at P314 (P = 0.0337);.;
MVP		0.60
MPC		0.49
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.58
gMVP		0.62

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: chr3-38416687;