rs12918539

Positions:

• chr16-17385538-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
XYLT1	NM_022166.4	c.364-27488G>A		intron_variant		ENST00000261381.7	NP_071449.1
XYLT1	XM_017023539.3	c.364-27488G>A		intron_variant			XP_016879028.1
XYLT1	XM_047434458.1	c.363+84896G>A		intron_variant			XP_047290414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7	c.364-27488G>A		intron_variant		1	NM_022166.4	ENSP00000261381	P1
XYLT1	ENST00000568226.5	n.56+17908G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.0409

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.330

Alfa AF: 0.327 Hom.: 1037

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

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

Other links and lift over

dbSNP: rs12918539; hg19: chr16-17479395;