chr3-38346887-C-A

Variant names:

• chr3-38346887-C-A
• rs773147579
• NM_005108.4:c.19C>A

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.19C>A​(p.Arg7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000731 in 1,367,506 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: XYLB NM_005108.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• 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=0.110637695).

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.19C>A	p.Arg7Ser	missense	Exon 1 of 19	NP_005099.2
	XYLB	NM_001349178.2		c.19C>A	p.Arg7Ser	missense	Exon 1 of 20	NP_001336107.1
	XYLB	NM_001349180.2		c.19C>A	p.Arg7Ser	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.19C>A	p.Arg7Ser	missense	Exon 1 of 19	ENSP00000207870.3	O75191-1
	XYLB	ENST00000854437.1		c.19C>A	p.Arg7Ser	missense	Exon 1 of 20	ENSP00000524496.1
	XYLB	ENST00000650590.1		c.19C>A	p.Arg7Ser	missense	Exon 1 of 18	ENSP00000496840.1	A0A3B3IRM4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.31e-7 AC: 1 AN: 1367506 Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1 AN XY: 675578

African (AFR) AF: 0.0000357 AC: 1 AN: 28046

American (AMR) AF: 0.00 AC: 0 AN: 32992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23976

East Asian (EAS) AF: 0.00 AC: 0 AN: 30978

South Asian (SAS) AF: 0.00 AC: 0 AN: 75968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45262

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068644

Other (OTH) AF: 0.00 AC: 0 AN: 56596

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.20	N
PhyloP100		1.0
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.30	N
REVEL	Benign	0.046
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.018	D
Polyphen		0.011	B
Vest4		0.22
MutPred		0.45		Gain of glycosylation at R7 (P = 0.0023)
MVP		0.11
MPC		0.11
ClinPred		0.079	T
GERP RS		1.7
PromoterAI		0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.36
gMVP		0.34
Mutation Taster		=89/11	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: rs773147579; hg19: chr3-38388378;