rs766521030

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_022166.4(XYLT1):c.154G>A(p.Gly52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,111,762 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00091 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0014 ( 6 hom. )

Consequence

XYLT1
NM_022166.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.110

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:

LOC107987234 (HGNC:):

LOC107987234 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004581392).

BP6

Variant 16-17470643-C-T is Benign according to our data. Variant chr16-17470643-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 577084.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000912 (134/146872) while in subpopulation SAS AF = 0.00167 (8/4792). AF 95% confidence interval is 0.00125. There are 1 homozygotes in GnomAd4. There are 62 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
XYLT1	NM_022166.4 link	c.154G>A	p.Gly52Ser	missense_variant	Exon 1 of 12	ENST00000261381.7	NP_071449.1
XYLT1	XM_047434458.1 link	c.154G>A	p.Gly52Ser	missense_variant	Exon 1 of 11		XP_047290414.1
XYLT1	XM_017023539.3 link	c.154G>A	p.Gly52Ser	missense_variant	Exon 1 of 12		XP_016879028.1
LOC107987234	XR_001752091.2 link	n.-216G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7 link	c.154G>A	p.Gly52Ser	missense_variant	Exon 1 of 12	1	NM_022166.4	ENSP00000261381.6

Frequencies

GnomAD3 genomes

AF:

0.000913

AC:

134

AN:

146762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000563

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00167

Gnomad FIN

AF:

0.000114

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00149

Gnomad OTH

AF:

0.000494

GnomAD2 exomes

AF:

0.00119

AC:

AN:

41118

AF XY:

0.00120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000149

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00155

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00142

AC:

1367

AN:

964890

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

669

AN XY:

466032

show subpopulations

African (AFR)

AF:

0.000219

AC:

AN:

18238

American (AMR)

AF:

0.000195

AC:

AN:

10272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10340

East Asian (EAS)

AF:

0.00

AC:

AN:

7314

South Asian (SAS)

AF:

0.00199

AC:

AN:

36696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9100

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2176

European-Non Finnish (NFE)

AF:

0.00149

AC:

1244

AN:

837258

Other (OTH)

AF:

0.00131

AC:

AN:

33496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

161

241

322

402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<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:

0.000912

AC:

134

AN:

146872

Hom.:

Cov.:

AF XY:

0.000867

AC XY:

AN XY:

71498

show subpopulations

African (AFR)

AF:

0.000562

AC:

AN:

40940

American (AMR)

AF:

0.000202

AC:

AN:

14834

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3390

East Asian (EAS)

AF:

0.00

AC:

AN:

4946

South Asian (SAS)

AF:

0.00167

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.000114

AC:

AN:

8752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00149

AC:

AN:

65978

Other (OTH)

AF:

0.000489

AC:

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00171

Hom.:

Bravo

AF:

0.000706

ExAC

AF:

0.000874

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jul 24, 2019

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge -

Desbuquois dysplasia 1

Benign:1

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

XYLT1-related disorder

Benign:1

May 23, 2022

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

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.012

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.039

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

PhyloP100

0.11

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.020

REVEL

Benign

0.027

Sift

Benign

0.20

Sift4G

Benign

0.65

Polyphen

0.0020

Vest4

0.074

MVP

0.068

MPC

0.22

ClinPred

0.014

GERP RS

0.46

PromoterAI

-0.033

Neutral

(source)

Varity_R

0.084

gMVP

0.30

Mutation Taster

=95/5

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

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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