chr16-17252379-A-G

Variant names:

• chr16-17252379-A-G
• rs1457907
• NM_022166.4:c.913+6609T>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.913+6609T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 151,888 control chromosomes in the GnomAD database, including 29,557 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 0.61 (29557 hom., cov: 31)
• Consequence: XYLT1 NM_022166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 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+6609T>C		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+6609T>C		intron	N/A	ENSP00000261381.6
	XYLT1	ENST00000575674.1	TSL:3	n.41+6609T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93087 AN: 151770 Hom.: 29503 Cov.: 31

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.614 AC: 93199 AN: 151888 Hom.: 29557 Cov.: 31 AF XY: 0.606 AC XY: 44995 AN XY: 74242

African (AFR) AF: 0.760 AC: 31479 AN: 41406

American (AMR) AF: 0.621 AC: 9481 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2171 AN: 3466

East Asian (EAS) AF: 0.234 AC: 1207 AN: 5160

South Asian (SAS) AF: 0.629 AC: 3013 AN: 4790

European-Finnish (FIN) AF: 0.459 AC: 4844 AN: 10554

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39099 AN: 67938

Other (OTH) AF: 0.601 AC: 1264 AN: 2104

Alfa AF: 0.597 Hom.: 87469

Bravo AF: 0.631

Asia WGS AF: 0.513 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.56
PhyloP100		0.091
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: rs1457907; hg19: chr16-17346236;