rs9933117

Variant names:

• chr16-17161714-T-C
• rs9933117
• NM_022166.4:c.1290-2805A>G

Variant summary

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

The NM_022166.4(XYLT1):​c.1290-2805A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 150,738 control chromosomes in the GnomAD database, including 35,388 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 0.68 (35388 hom., cov: 29)
• Consequence: XYLT1 NM_022166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XYLT1	NM_022166.4	c.1290-2805A>G		intron_variant	Intron 5 of 11	ENST00000261381.7	NP_071449.1
XYLT1	XM_047434458.1	c.1251-2805A>G		intron_variant	Intron 4 of 10		XP_047290414.1
XYLT1	XM_017023539.3	c.1290-2805A>G		intron_variant	Intron 5 of 11		XP_016879028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7	c.1290-2805A>G		intron_variant	Intron 5 of 11	1	NM_022166.4	ENSP00000261381.6

Frequencies

GnomAD3 genomes AF: 0.682 AC: 102784 AN: 150618 Hom.: 35384 Cov.: 29

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.682 AC: 102813 AN: 150738 Hom.: 35388 Cov.: 29 AF XY: 0.676 AC XY: 49680 AN XY: 73544

African (AFR) AF: 0.632 AC: 25975 AN: 41082

American (AMR) AF: 0.584 AC: 8857 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2253 AN: 3444

East Asian (EAS) AF: 0.753 AC: 3851 AN: 5114

South Asian (SAS) AF: 0.462 AC: 2182 AN: 4726

European-Finnish (FIN) AF: 0.713 AC: 7299 AN: 10238

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50214 AN: 67686

Other (OTH) AF: 0.689 AC: 1446 AN: 2098

Alfa AF: 0.711 Hom.: 49095

Bravo AF: 0.671

Asia WGS AF: 0.607 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.022
DANN	Benign	0.29
PhyloP100		-2.7
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: rs9933117; hg19: chr16-17255571;