rs12918539

Variant names:

• chr16-17385538-C-T
• rs12918539
• NM_022166.4:c.364-27488G>A

Variant summary

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

The NM_022166.4(XYLT1):​c.364-27488G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,680 control chromosomes in the GnomAD database, including 7,595 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 0.30 (7595 hom., cov: 32)
• Consequence: XYLT1 NM_022166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.54
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XYLT1	NM_022166.4	c.364-27488G>A		intron_variant	Intron 1 of 11	ENST00000261381.7	NP_071449.1
XYLT1	XM_047434458.1	c.363+84896G>A		intron_variant	Intron 1 of 10		XP_047290414.1
XYLT1	XM_017023539.3	c.364-27488G>A		intron_variant	Intron 1 of 11		XP_016879028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7	c.364-27488G>A		intron_variant	Intron 1 of 11	1	NM_022166.4	ENSP00000261381.6
XYLT1	ENST00000568226.5	n.56+17908G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45833 AN: 151562 Hom.: 7598 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.302 AC: 45835 AN: 151680 Hom.: 7595 Cov.: 32 AF XY: 0.290 AC XY: 21500 AN XY: 74100

African (AFR) AF: 0.243 AC: 10068 AN: 41452

American (AMR) AF: 0.252 AC: 3818 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1331 AN: 3472

East Asian (EAS) AF: 0.0409 AC: 205 AN: 5018

South Asian (SAS) AF: 0.248 AC: 1192 AN: 4810

European-Finnish (FIN) AF: 0.261 AC: 2746 AN: 10506

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25409 AN: 67984

Other (OTH) AF: 0.330 AC: 696 AN: 2112

Alfa AF: 0.324 Hom.: 1058

Bravo AF: 0.298

Asia WGS AF: 0.156 AC: 541 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.012
DANN	Benign	0.63
PhyloP100		-5.5
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: rs12918539; hg19: chr16-17479395;