16-17134493-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS1

The NM_022166.4(XYLT1):c.2007G>A(p.Thr669Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000859 in 1,614,106 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 0.00065 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 1 hom. )

Consequence

XYLT1
NM_022166.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -4.99

Publications

0 publications found

Variant links:

Genes affected

XYLT1 (HGNC:15516): (xylosyltransferase 1) This locus encodes a xylosyltransferase enzyme. The encoded protein catalyzes transfer of UDP-xylose to serine residues of an acceptor protein substrate. This transfer reaction is necessary for biosynthesis of glycosaminoglycan chains. Mutations in this gene have been associated with increased severity of pseudoxanthoma elasticum.[provided by RefSeq, Nov 2009]

XYLT1 Gene-Disease associations (from GenCC):

Desbuquois dysplasia 2
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Desbuquois dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
XYLT1-congenital disorder of glycosylation
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

XYLT1 links:

ENSG00000261448 (HGNC:):

ENSG00000261448 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 16-17134493-C-T is Benign according to our data. Variant chr16-17134493-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 541799.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.99 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00065 (99/152276) while in subpopulation NFE AF = 0.00104 (71/68012). AF 95% confidence interval is 0.000848. There are 0 homozygotes in GnomAd4. There are 38 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
XYLT1	NM_022166.4 link	c.2007G>A	p.Thr669Thr	synonymous_variant	Exon 9 of 12	ENST00000261381.7	NP_071449.1
XYLT1	XM_047434458.1 link	c.1968G>A	p.Thr656Thr	synonymous_variant	Exon 8 of 11		XP_047290414.1
XYLT1	XM_017023539.3 link	c.2007G>A	p.Thr669Thr	synonymous_variant	Exon 9 of 12		XP_016879028.1
LOC102723692	NR_135179.1 link	n.-11C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7 link	c.2007G>A	p.Thr669Thr	synonymous_variant	Exon 9 of 12	1	NM_022166.4	ENSP00000261381.6

Frequencies

GnomAD3 genomes

AF:

0.000651

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.00104

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000793

AC:

199

AN:

250894

AF XY:

0.000737

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.000371

Gnomad NFE exome

AF:

0.00127

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.000880

AC:

1287

AN:

1461830

Hom.:

Cov.:

AF XY:

0.000850

AC XY:

618

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.000358

AC:

AN:

33480

American (AMR)

AF:

0.000716

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000712

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00103

AC:

1145

AN:

1112010

Other (OTH)

AF:

0.000679

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

155

233

310

388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

138

184

230

<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:

0.000650

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41546

American (AMR)

AF:

0.000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00104

AC:

AN:

68012

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.000920

Hom.:

Bravo

AF:

0.000714

EpiCase

AF:

0.00125

EpiControl

AF:

0.00101

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Desbuquois dysplasia 1

Benign:1

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

XYLT1-related disorder

Benign:1

Dec 19, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

-0.60

CADD

Benign

1.7

(source)

DANN

Benign

0.93

PhyloP100

-5.0

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over