Variant 16-17134493-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_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

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:

ENSG00000261448 (HGNC:):

ENSG00000261448 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XYLT1	NM_022166.4 linkuse as main transcript	c.2007G>A	p.Thr669Thr	synonymous_variant	9/12	ENST00000261381.7	NP_071449.1	Q86Y38
XYLT1	XM_047434458.1 linkuse as main transcript	c.1968G>A	p.Thr656Thr	synonymous_variant	8/11		XP_047290414.1
XYLT1	XM_017023539.3 linkuse as main transcript	c.2007G>A	p.Thr669Thr	synonymous_variant	9/12		XP_016879028.1
LOC102723692	NR_135179.1 linkuse as main transcript	n.-11C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7 linkuse as main transcript	c.2007G>A	p.Thr669Thr	synonymous_variant	9/12	1	NM_022166.4	ENSP00000261381.6		Q86Y38
ENSG00000261448	ENST00000567344.1 linkuse as main transcript	n.-11C>T		upstream_gene_variant		3

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

GnomAD3 exomes

AF:

0.000793

AC:

199

AN:

250894

Hom.:

AF XY:

0.000737

AC XY:

100

AN XY:

135638

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 SAS exome

AF:

0.0000980

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

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.000712

Gnomad4 NFE exome

AF:

0.00103

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.000650

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.000474

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 09, 2024

- -

XYLT1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 19, 2023

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

DANN

Benign

0.93

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