rs752482

Variant names:

• chr16-17177470-T-C
• rs752482
• NM_022166.4:c.1290-18561A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022166.4(XYLT1):​c.1290-18561A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,932 control chromosomes in the GnomAD database, including 4,300 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4300 hom., cov: 32)
• Consequence: XYLT1 NM_022166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XYLT1	NM_022166.4	c.1290-18561A>G		intron_variant	Intron 5 of 11	ENST00000261381.7	NP_071449.1
XYLT1	XM_047434458.1	c.1251-18561A>G		intron_variant	Intron 4 of 10		XP_047290414.1
XYLT1	XM_017023539.3	c.1290-18561A>G		intron_variant	Intron 5 of 11		XP_016879028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7	c.1290-18561A>G		intron_variant	Intron 5 of 11	1	NM_022166.4	ENSP00000261381.6

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33698 AN: 151814 Hom.: 4289 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.193

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.222 AC: 33750 AN: 151932 Hom.: 4300 Cov.: 32 AF XY: 0.225 AC XY: 16727 AN XY: 74284

African (AFR) AF: 0.342 AC: 14109 AN: 41304

American (AMR) AF: 0.128 AC: 1959 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3472

East Asian (EAS) AF: 0.194 AC: 1004 AN: 5174

South Asian (SAS) AF: 0.233 AC: 1124 AN: 4814

European-Finnish (FIN) AF: 0.276 AC: 2926 AN: 10590

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11262 AN: 67988

Other (OTH) AF: 0.192 AC: 405 AN: 2110

Alfa AF: 0.180 Hom.: 8558

Bravo AF: 0.214

Asia WGS AF: 0.224 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.64
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs752482; hg19: chr16-17271327;