NM_022166.4:c.343G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022166.4(XYLT1):c.343G>T(p.Ala115Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 1,230,650 control chromosomes in the GnomAD database, including 523 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 49 hom., cov: 31)

Exomes 𝑓: 0.028 ( 474 hom. )

Consequence

XYLT1
NM_022166.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 0.397

Publications

19 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013451189).

BP6

Variant 16-17470454-C-A is Benign according to our data. Variant chr16-17470454-C-A is described in ClinVar as Benign. ClinVar VariationId is 2534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0187 (2844/151954) while in subpopulation NFE AF = 0.0293 (1989/67872). AF 95% confidence interval is 0.0282. There are 49 homozygotes in GnomAd4. There are 1313 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XYLT1	NM_022166.4 link	c.343G>T	p.Ala115Ser	missense_variant	Exon 1 of 12	ENST00000261381.7	NP_071449.1	Q86Y38
XYLT1	XM_047434458.1 link	c.343G>T	p.Ala115Ser	missense_variant	Exon 1 of 11		XP_047290414.1
XYLT1	XM_017023539.3 link	c.343G>T	p.Ala115Ser	missense_variant	Exon 1 of 12		XP_016879028.1
LOC107987234	XR_001752091.2 link	n.-27G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7 link	c.343G>T	p.Ala115Ser	missense_variant	Exon 1 of 12	1	NM_022166.4	ENSP00000261381.6		Q86Y38

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2845

AN:

151840

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00524

Gnomad AMI

AF:

0.0747

Gnomad AMR

AF:

0.0182

Gnomad ASJ

AF:

0.0346

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00890

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0293

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0273

AC:

AN:

988

AF XY:

0.0234

show subpopulations

Gnomad AFR exome

AF:

0.0250

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0357

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0297

Gnomad OTH exome

AF:

0.0294

GnomAD4 exome

AF:

0.0280

AC:

30184

AN:

1078696

Hom.:

474

Cov.:

AF XY:

0.0279

AC XY:

14220

AN XY:

510138

show subpopulations

African (AFR)

AF:

0.00374

AC:

AN:

22736

American (AMR)

AF:

0.0114

AC:

AN:

8306

Ashkenazi Jewish (ASJ)

AF:

0.0329

AC:

466

AN:

14180

East Asian (EAS)

AF:

0.00

AC:

AN:

26402

South Asian (SAS)

AF:

0.00455

AC:

AN:

20234

European-Finnish (FIN)

AF:

0.00807

AC:

170

AN:

21072

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

3232

European-Non Finnish (NFE)

AF:

0.0307

AC:

28176

AN:

919108

Other (OTH)

AF:

0.0238

AC:

1034

AN:

43426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1828

3656

5484

7312

9140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1234

2468

3702

4936

6170

<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:

0.0187

AC:

2844

AN:

151954

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1313

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.00522

AC:

217

AN:

41540

American (AMR)

AF:

0.0181

AC:

277

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0346

AC:

120

AN:

3464

East Asian (EAS)

AF:

0.000196

AC:

AN:

5106

South Asian (SAS)

AF:

0.00518

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00890

AC:

AN:

10558

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0293

AC:

1989

AN:

67872

Other (OTH)

AF:

0.0223

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

141

282

424

565

706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0161

Hom.:

Bravo

AF:

0.0181

ExAC

AF:

0.00598

AC:

316

Asia WGS

AF:

0.00289

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 30, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 19014925, 16759312, 16571645) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Desbuquois dysplasia 2

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Desbuquois dysplasia 1

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive inherited pseudoxanthoma elasticum;C4014294:Desbuquois dysplasia 2

Benign:1

Feb 06, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

PSEUDOXANTHOMA ELASTICUM, MODIFIER OF SEVERITY OF

Other:1

Sep 01, 2006

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0093

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.36

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PhyloP100

0.40

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.010

REVEL

Benign

0.021

Sift

Benign

0.41

Sift4G

Benign

0.50

Polyphen

0.0010

Vest4

0.024

MPC

0.20

ClinPred

0.0042

GERP RS

1.8

Varity_R

0.082

gMVP

0.12

Mutation Taster

=98/2

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