16-17246079-C-T

Position:

• chr16-17246079-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.913+12909G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,138 control chromosomes in the GnomAD database, including 7,105 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 0.28 (7105 hom., cov: 32)
• Consequence: XYLT1 NM_022166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XYLT1	NM_022166.4	c.913+12909G>A		intron_variant		ENST00000261381.7
XYLT1	XM_017023539.3	c.913+12909G>A		intron_variant
XYLT1	XM_047434458.1	c.874+12909G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XYLT1	ENST00000261381.7	c.913+12909G>A		intron_variant		1	NM_022166.4	P1
XYLT1	ENST00000575674.1	n.41+12909G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42904 AN: 152020 Hom.: 7109 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.282 AC: 42904 AN: 152138 Hom.: 7105 Cov.: 32 AF XY: 0.276 AC XY: 20501 AN XY: 74370

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.295

Alfa AF: 0.349 Hom.: 5538

Bravo AF: 0.272

Asia WGS AF: 0.263 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.68
DANN	Benign	0.72

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: rs12918720; hg19: chr16-17339936;