Genetic Variant XYLT2:p.Ala3Gly (chr17-50346148-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022167.4(XYLT2):c.8C>G(p.Ala3Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000901 in 1,109,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A3V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 9.0e-7 ( 0 hom. )

Consequence

XYLT2
NM_022167.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.53

Publications

0 publications found

Variant links:

Genes affected

XYLT2 (HGNC:15517): (xylosyltransferase 2) The protein encoded by this gene is an isoform of xylosyltransferase, which belongs to a family of glycosyltransferases. This enzyme transfers xylose from UDP-xylose to specific serine residues of the core protein and initiates the biosynthesis of glycosaminoglycan chains in proteoglycans including chondroitin sulfate, heparan sulfate, heparin and dermatan sulfate. The enzyme activity, which is increased in scleroderma patients, is a diagnostic marker for the determination of sclerotic activity in systemic sclerosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2013]

XYLT2 Gene-Disease associations (from GenCC):

spondylo-ocular syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

XYLT2 links:

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ACMG classification

Classification was made for transcript

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=0.23557127).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022167.4. 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
	XYLT2	NM_022167.4	MANE Select	c.8C>G	p.Ala3Gly	missense	Exon 1 of 11	NP_071450.2	Q9H1B5-1
	XYLT2	NR_110010.2		n.23C>G		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XYLT2	ENST00000017003.7	TSL:1 MANE Select	c.8C>G	p.Ala3Gly	missense	Exon 1 of 11	ENSP00000017003.2	Q9H1B5-1
XYLT2	ENST00000376550.7	TSL:1	n.8C>G		non_coding_transcript_exon	Exon 1 of 10	ENSP00000365733.3	A0A0C4DFW8
XYLT2	ENST00000854775.1		c.8C>G	p.Ala3Gly	missense	Exon 1 of 11	ENSP00000524834.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.01e-7

AC:

AN:

1109510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

545704

show subpopulations

African (AFR)

AF:

0.0000466

AC:

AN:

21440

American (AMR)

AF:

0.00

AC:

AN:

18562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15580

East Asian (EAS)

AF:

0.00

AC:

AN:

15938

South Asian (SAS)

AF:

0.00

AC:

AN:

58962

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2848

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

909974

Other (OTH)

AF:

0.00

AC:

AN:

39972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

Eigen

Benign

-0.060

Eigen_PC

Benign

0.0080

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

PhyloP100

4.5

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.30

REVEL

Benign

0.14

Sift

Uncertain

0.027

Sift4G

Benign

0.34

Polyphen

0.89

Vest4

0.41

MutPred

0.17

Gain of relative solvent accessibility (P = 0.0479)

MVP

0.21

MPC

0.71

ClinPred

0.93

GERP RS

3.2

PromoterAI

-0.50

Neutral

(source)

Varity_R

0.35

gMVP

0.54

Mutation Taster

=51/49

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over