17-50353668-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_022167.4(XYLT2):c.174C>T(p.Gly58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,567,110 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (2 hom.)
• Consequence: XYLT2 NM_022167.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.48

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 17-50353668-C-T is Benign according to our data. Variant chr17-50353668-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1654629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.48 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000854 (13/152268) while in subpopulation SAS AF= 0.00166 (8/4824). AF 95% confidence interval is 0.000825. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XYLT2	NM_022167.4	c.174C>T	p.Gly58=	synonymous_variant	2/11	ENST00000017003.7
XYLT2	XM_005257572.5	c.78C>T	p.Gly26=	synonymous_variant	2/11
XYLT2	XM_047436522.1	c.-418C>T		5_prime_UTR_variant	2/11
XYLT2	NR_110010.2	n.189C>T		non_coding_transcript_exon_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XYLT2	ENST00000017003.7	c.174C>T	p.Gly58=	synonymous_variant	2/11	1	NM_022167.4	P1
XYLT2	ENST00000376550.7	c.174C>T	p.Gly58=	synonymous_variant, NMD_transcript_variant	2/10	1
XYLT2	ENST00000507602.5	c.174C>T	p.Gly58=	synonymous_variant	2/10	2
XYLT2	ENST00000509778.1	c.129C>T	p.Gly43=	synonymous_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000267 AC: 47 AN: 176250 Hom.: 1 AF XY: 0.000340 AC XY: 32 AN XY: 94218

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000369

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00165

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000841

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000122 AC: 173 AN: 1414842 Hom.: 2 Cov.: 32 AF XY: 0.000166 AC XY: 116 AN XY: 699480

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000262

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000268

Gnomad4 SAS exome AF: 0.00136

Gnomad4 FIN exome AF: 0.0000200

Gnomad4 NFE exome AF: 0.0000396

Gnomad4 OTH exome AF: 0.000290

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152268 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74438

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.0000378

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 12, 2023

- -

XYLT2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 26, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	5.4
Dann	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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

Other links and lift over

dbSNP: rs530027095; hg19: chr17-48431029;