Genetic Variant NM_022167.4:c.32T>G (chr17-50346172-T-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.32T>G(p.Val11Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,286,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

XYLT2
NM_022167.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.71

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:

Genome browser will be placed here

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=0.214261).

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.32T>G	p.Val11Gly	missense	Exon 1 of 11	NP_071450.2	Q9H1B5-1
	XYLT2	NR_110010.2		n.47T>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.32T>G	p.Val11Gly	missense	Exon 1 of 11	ENSP00000017003.2	Q9H1B5-1
XYLT2	ENST00000376550.7	TSL:1	n.32T>G		non_coding_transcript_exon	Exon 1 of 10	ENSP00000365733.3	A0A0C4DFW8
XYLT2	ENST00000854775.1		c.32T>G	p.Val11Gly	missense	Exon 1 of 11	ENSP00000524834.1

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

147874

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000176

AC:

AN:

1138470

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

560950

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21938

American (AMR)

AF:

0.00

AC:

AN:

20154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16512

East Asian (EAS)

AF:

0.00

AC:

AN:

17188

South Asian (SAS)

AF:

0.00

AC:

AN:

63260

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29872

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3070

European-Non Finnish (NFE)

AF:

0.00000216

AC:

AN:

924988

Other (OTH)

AF:

0.00

AC:

AN:

41488

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

AF:

0.0000135

AC:

AN:

147874

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71992

show subpopulations

African (AFR)

AF:

0.0000244

AC:

AN:

41026

American (AMR)

AF:

0.00

AC:

AN:

14870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3408

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8964

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66382

Other (OTH)

AF:

0.00

AC:

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.095

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.64

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

1.7

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.33

Sift

Benign

0.59

Sift4G

Benign

0.43

Polyphen

0.0

Vest4

0.39

MutPred

0.45

Loss of stability (P = 0.0116)

MVP

0.21

MPC

0.54

ClinPred

0.26

GERP RS

3.1

PromoterAI

0.061

Neutral

(source)

Varity_R

0.25

gMVP

0.56

Mutation Taster

=73/27

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over