NM_022166.4:c.1290-18029A>C

Variant names:

• chr16-17176938-T-G
• rs936347
• NM_022166.4:c.1290-18029A>C

Variant summary

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

The NM_022166.4(XYLT1):​c.1290-18029A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,754 control chromosomes in the GnomAD database, including 29,703 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 0.60 (29703 hom., cov: 30)
• Consequence: XYLT1 NM_022166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XYLT1	NM_022166.4	c.1290-18029A>C		intron_variant	Intron 5 of 11	ENST00000261381.7	NP_071449.1
XYLT1	XM_047434458.1	c.1251-18029A>C		intron_variant	Intron 4 of 10		XP_047290414.1
XYLT1	XM_017023539.3	c.1290-18029A>C		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.1290-18029A>C		intron_variant	Intron 5 of 11	1	NM_022166.4	ENSP00000261381.6

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91006 AN: 151636 Hom.: 29623 Cov.: 30

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.601 AC: 91144 AN: 151754 Hom.: 29703 Cov.: 30 AF XY: 0.605 AC XY: 44831 AN XY: 74152

African (AFR) AF: 0.855 AC: 35369 AN: 41354

American (AMR) AF: 0.586 AC: 8932 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1990 AN: 3468

East Asian (EAS) AF: 0.373 AC: 1918 AN: 5144

South Asian (SAS) AF: 0.736 AC: 3544 AN: 4818

European-Finnish (FIN) AF: 0.567 AC: 5965 AN: 10516

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31596 AN: 67898

Other (OTH) AF: 0.550 AC: 1163 AN: 2114

Alfa AF: 0.540 Hom.: 5738

Bravo AF: 0.607

Asia WGS AF: 0.583 AC: 2026 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.76
PhyloP100		-0.51
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: rs936347; hg19: chr16-17270795;