chr17-50353652-G-A

Position:

chr17-50353652-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting

The NM_022167.4(XYLT2):c.158G>A(p.Arg53Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00003 in 1,565,918 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 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

XYLT2
NM_022167.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

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 links:

XYLT2 (HGNC:):

XYLT2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08362445).

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000526 (8/152184) while in subpopulation EAS AF= 0.000964 (5/5186). AF 95% confidence interval is 0.00038. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XYLT2	NM_022167.4 linkuse as main transcript	c.158G>A	p.Arg53Gln	missense_variant	2/11	ENST00000017003.7	NP_071450.2	Q9H1B5-1B4DT06
XYLT2	XM_005257572.5 linkuse as main transcript	c.62G>A	p.Arg21Gln	missense_variant	2/11		XP_005257629.1
XYLT2	XM_047436522.1 linkuse as main transcript	c.-434G>A		5_prime_UTR_variant	2/11		XP_047292478.1
XYLT2	NR_110010.2 linkuse as main transcript	n.173G>A		non_coding_transcript_exon_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
XYLT2	ENST00000017003.7 linkuse as main transcript	c.158G>A	p.Arg53Gln	missense_variant	2/11	1	NM_022167.4	ENSP00000017003.2	Q9H1B5-1
XYLT2	ENST00000376550.7 linkuse as main transcript	n.158G>A		non_coding_transcript_exon_variant	2/10	1		ENSP00000365733.3	A0A0C4DFW8
XYLT2	ENST00000507602.5 linkuse as main transcript	c.158G>A	p.Arg53Gln	missense_variant	2/10	2		ENSP00000426501.1	B4DT06
XYLT2	ENST00000509778.1 linkuse as main transcript	c.113G>A	p.Arg38Gln	missense_variant	2/2	3		ENSP00000425511.1	D6RCT0

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000516

AC:

AN:

174258

Hom.:

AF XY:

0.0000537

AC XY:

AN XY:

93172

show subpopulations

Gnomad AFR exome

AF:

0.0000984

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000226

Gnomad SAS exome

AF:

0.000208

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000276

AC:

AN:

1413734

Hom.:

Cov.:

AF XY:

0.0000258

AC XY:

AN XY:

698822

show subpopulations

Gnomad4 AFR exome

AF:

0.0000619

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000350

Gnomad4 SAS exome

AF:

0.000161

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000921

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000336

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.158G>A (p.R53Q) alteration is located in exon 2 (coding exon 2) of the XYLT2 gene. This alteration results from a G to A substitution at nucleotide position 158, causing the arginine (R) at amino acid position 53 to be replaced by a glutamine (Q). 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

Benign

0.082

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

T;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.056

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.84

T;D;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.084

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.41

N;.;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.5

N;D;N

REVEL

Benign

0.050

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.059

B;.;.

Vest4

0.26

MutPred

0.16

Gain of methylation at K51 (P = 0.0715);.;Gain of methylation at K51 (P = 0.0715);

MVP

0.33

MPC

0.48

ClinPred

0.048

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.064

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over