rs1457907

Positions:

• chr16-17252379-A-G

Variant summary

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

The NM_022166.4(XYLT1):​c.913+6609T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 151,888 control chromosomes in the GnomAD database, including 29,557 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 0.61 (29557 hom., cov: 31)
• Consequence: XYLT1 NM_022166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XYLT1	NM_022166.4	c.913+6609T>C		intron_variant		ENST00000261381.7
XYLT1	XM_017023539.3	c.913+6609T>C		intron_variant
XYLT1	XM_047434458.1	c.874+6609T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XYLT1	ENST00000261381.7	c.913+6609T>C		intron_variant		1	NM_022166.4	P1
XYLT1	ENST00000575674.1	n.41+6609T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93087 AN: 151770 Hom.: 29503 Cov.: 31

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.614 AC: 93199 AN: 151888 Hom.: 29557 Cov.: 31 AF XY: 0.606 AC XY: 44995 AN XY: 74242

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.601

Alfa AF: 0.587 Hom.: 53454

Bravo AF: 0.631

Asia WGS AF: 0.513 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.56

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: rs1457907; hg19: chr16-17346236;