rs12918720

Variant names:

• chr16-17246079-C-T
• rs12918720
• NM_022166.4:c.913+12909G>A

Variant summary

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

The ENST00000261381.7(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 ENST00000261381.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000261381.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLT1	NM_022166.4	MANE Select	c.913+12909G>A		intron	N/A	NP_071449.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLT1	ENST00000261381.7	TSL:1 MANE Select	c.913+12909G>A		intron	N/A	ENSP00000261381.6
	XYLT1	ENST00000575674.1	TSL:3	n.41+12909G>A		intron	N/A

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

African (AFR) AF: 0.125 AC: 5174 AN: 41532

American (AMR) AF: 0.261 AC: 3997 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1369 AN: 3464

East Asian (EAS) AF: 0.108 AC: 560 AN: 5176

South Asian (SAS) AF: 0.371 AC: 1788 AN: 4820

European-Finnish (FIN) AF: 0.262 AC: 2768 AN: 10578

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26061 AN: 67968

Other (OTH) AF: 0.295 AC: 623 AN: 2110

Alfa AF: 0.342 Hom.: 7459

Bravo AF: 0.272

Asia WGS AF: 0.263 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.68
DANN	Benign	0.72
PhyloP100		-1.0
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: rs12918720; hg19: chr16-17339936;