17-50346155-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1

The NM_022167.4(XYLT2):c.15G>A(p.Ala5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000664 in 1,267,174 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 0 hom. )

Consequence

XYLT2
NM_022167.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0200

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 17-50346155-G-A is Benign according to our data. Variant chr17-50346155-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1664871.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.02 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000656 (97/147922) while in subpopulation NFE AF= 0.00128 (85/66352). AF 95% confidence interval is 0.00106. There are 1 homozygotes in gnomad4. There are 42 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 linkuse as main transcript	c.15G>A	p.Ala5=	synonymous_variant	1/11	ENST00000017003.7
XYLT2	NR_110010.2 linkuse as main transcript	n.30G>A		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XYLT2	ENST00000017003.7 linkuse as main transcript	c.15G>A	p.Ala5=	synonymous_variant	1/11	1	NM_022167.4	P1	Q9H1B5-1
XYLT2	ENST00000376550.7 linkuse as main transcript	c.15G>A	p.Ala5=	synonymous_variant, NMD_transcript_variant	1/10	1
XYLT2	ENST00000507602.5 linkuse as main transcript	c.15G>A	p.Ala5=	synonymous_variant	1/10	2
XYLT2	ENST00000509778.1 linkuse as main transcript	c.15G>A	p.Ala5=	synonymous_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.000656

AC:

AN:

147922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000672

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00100

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.000490

GnomAD3 exomes

AF:

0.000428

AC:

AN:

79514

Hom.:

AF XY:

0.000354

AC XY:

AN XY:

45242

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000746

Gnomad ASJ exome

AF:

0.000151

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000482

Gnomad NFE exome

AF:

0.000946

Gnomad OTH exome

AF:

0.000459

GnomAD4 exome

AF:

0.000665

AC:

744

AN:

1119252

Hom.:

Cov.:

AF XY:

0.000650

AC XY:

358

AN XY:

551014

show subpopulations

Gnomad4 AFR exome

AF:

0.000139

Gnomad4 AMR exome

AF:

0.0000520

Gnomad4 ASJ exome

AF:

0.0000629

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00131

Gnomad4 NFE exome

AF:

0.000754

Gnomad4 OTH exome

AF:

0.000321

GnomAD4 genome

AF:

0.000656

AC:

AN:

147922

Hom.:

Cov.:

AF XY:

0.000583

AC XY:

AN XY:

72014

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.0000672

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00100

Gnomad4 NFE

AF:

0.00128

Gnomad4 OTH

AF:

0.000490

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.000518

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

Cadd

Benign

Dann

Uncertain

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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