rs12931053

Variant names:

• chr16-17275463-G-A
• rs12931053
• NM_022166.4:c.403-15965C>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.403-15965C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,962 control chromosomes in the GnomAD database, including 5,455 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 0.26 (5455 hom., cov: 31)
• Consequence: XYLT1 NM_022166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347
• Publications: 0 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XYLT1	NM_022166.4	c.403-15965C>T		intron_variant	Intron 2 of 11	ENST00000261381.7	NP_071449.1
XYLT1	XM_047434458.1	c.364-15965C>T		intron_variant	Intron 1 of 10		XP_047290414.1
XYLT1	XM_017023539.3	c.403-15965C>T		intron_variant	Intron 2 of 11		XP_016879028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7	c.403-15965C>T		intron_variant	Intron 2 of 11	1	NM_022166.4	ENSP00000261381.6

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39588 AN: 151842 Hom.: 5457 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.0579

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.261 AC: 39594 AN: 151962 Hom.: 5455 Cov.: 31 AF XY: 0.255 AC XY: 18949 AN XY: 74298

African (AFR) AF: 0.304 AC: 12607 AN: 41414

American (AMR) AF: 0.223 AC: 3409 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1460 AN: 3472

East Asian (EAS) AF: 0.0577 AC: 298 AN: 5168

South Asian (SAS) AF: 0.299 AC: 1441 AN: 4820

European-Finnish (FIN) AF: 0.158 AC: 1675 AN: 10584

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.263 AC: 17832 AN: 67928

Other (OTH) AF: 0.290 AC: 613 AN: 2112

Alfa AF: 0.251 Hom.: 1646

Bravo AF: 0.263

Asia WGS AF: 0.209 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.27
PhyloP100		-0.35
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: rs12931053; hg19: chr16-17369320;