rs722075

Positions:

• chr16-17240642-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022166.4(XYLT1):​c.913+18346C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,078 control chromosomes in the GnomAD database, including 2,653 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 0.18 (2653 hom., cov: 32)
• Consequence: XYLT1 NM_022166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XYLT1	NM_022166.4	c.913+18346C>T		intron_variant		ENST00000261381.7	NP_071449.1
XYLT1	XM_017023539.3	c.913+18346C>T		intron_variant			XP_016879028.1
XYLT1	XM_047434458.1	c.874+18346C>T		intron_variant			XP_047290414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7	c.913+18346C>T		intron_variant		1	NM_022166.4	ENSP00000261381	P1
XYLT1	ENST00000575674.1	n.41+18346C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27816 AN: 151960 Hom.: 2638 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.183 AC: 27857 AN: 152078 Hom.: 2653 Cov.: 32 AF XY: 0.183 AC XY: 13583 AN XY: 74336

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.169

Alfa AF: 0.184 Hom.: 3607

Bravo AF: 0.175

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.77

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: rs722075; hg19: chr16-17334499;