rs61758388

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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:4O:1

Conservation

PhyloP100: 0.397

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 links:

LOC107987234 (HGNC:):

LOC107987234 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 2534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-17470454-C-A is described in Lovd as [Benign]. Variant chr16-17470454-C-A is described in Lovd as [Likely_benign]. Variant chr16-17470454-C-A is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
XYLT1	NM_022166.4 linkuse as main transcript	c.343G>T	p.Ala115Ser	missense_variant	1/12	ENST00000261381.7	NP_071449.1
XYLT1	XM_047434458.1 linkuse as main transcript	c.343G>T	p.Ala115Ser	missense_variant	1/11		XP_047290414.1
XYLT1	XM_017023539.3 linkuse as main transcript	c.343G>T	p.Ala115Ser	missense_variant	1/12		XP_016879028.1
LOC107987234	XR_001752091.2 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7 linkuse as main transcript	c.343G>T	p.Ala115Ser	missense_variant	1/12	1	NM_022166.4	ENSP00000261381	P1

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

GnomAD3 exomes

AF:

0.0273

AC:

AN:

988

Hom.:

AF XY:

0.0234

AC XY:

AN XY:

556

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 SAS 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

Gnomad4 AFR exome

AF:

0.00374

Gnomad4 AMR exome

AF:

0.0114

Gnomad4 ASJ exome

AF:

0.0329

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00455

Gnomad4 FIN exome

AF:

0.00807

Gnomad4 NFE exome

AF:

0.0307

Gnomad4 OTH exome

AF:

0.0238

GnomAD4 genome

AF:

0.0187

AC:

2844

AN:

151954

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1313

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.00522

Gnomad4 AMR

AF:

0.0181

Gnomad4 ASJ

AF:

0.0346

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00890

Gnomad4 NFE

AF:

0.0293

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.0119

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:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 30, 2020	This variant is associated with the following publications: (PMID: 19014925, 16759312, 16571645) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Desbuquois dysplasia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Desbuquois dysplasia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Pseudoxanthoma elasticum, modifier of severity of

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Sep 01, 2006

- -

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

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

MutationTaster

Benign

0.051

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

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

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