16-17134493-C-T

Variant names:

• chr16-17134493-C-T
• rs150492983
• NM_022166.4:c.2007G>A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2 BP4_Strong BP6_Moderate BP7 BS1

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
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -4.99

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]

ENSG00000261448 (HGNC:):

ACMG classification

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7	c.2007G>A	p.Thr669Thr	synonymous_variant	Exon 9 of 12	1	NM_022166.4	ENSP00000261381.6
ENSG00000261448	ENST00000567344.1	n.-11C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 99 AN: 152158 Hom.: 0 Cov.: 32

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.: 0 AF XY: 0.000737 AC XY: 100 AN XY: 135638

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.: 1 Cov.: 30 AF XY: 0.000850 AC XY: 618 AN XY: 727214

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: 99 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38 AN XY: 74454

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.: 0

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

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
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

Other links and lift over

dbSNP: rs150492983; hg19: chr16-17228350;