16-17240642-G-A

Variant names:

• chr16-17240642-G-A
• rs722075
• NM_022166.4:c.913+18346C>T

Variant summary

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022166.4. 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+18346C>T		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+18346C>T		intron	N/A	ENSP00000261381.6
	XYLT1	ENST00000575674.1	TSL:3	n.41+18346C>T		intron	N/A

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

African (AFR) AF: 0.194 AC: 8050 AN: 41488

American (AMR) AF: 0.125 AC: 1911 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3468

East Asian (EAS) AF: 0.106 AC: 548 AN: 5182

South Asian (SAS) AF: 0.133 AC: 641 AN: 4820

European-Finnish (FIN) AF: 0.241 AC: 2541 AN: 10560

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13217 AN: 67954

Other (OTH) AF: 0.169 AC: 358 AN: 2114

Alfa AF: 0.186 Hom.: 8139

Bravo AF: 0.175

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.77
PhyloP100		-0.29
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: rs722075; hg19: chr16-17334499;