rs1085307563

Variant names:

• chr16-17138385-G-GTCAT
• rs1085307563
• NM_022166.4:c.1730_1733dupATGA

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_022166.4(XYLT1):​c.1730_1733dupATGA​(p.Asp578GlufsTer2) variant causes a frameshift, stop gained change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: XYLT1 NM_022166.4 frameshift, stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 6.01

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]

ENSG00000261448 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-17138385-G-GTCAT is Pathogenic according to our data. Variant chr16-17138385-G-GTCAT is described in ClinVar as [Pathogenic]. Clinvar id is 426319.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XYLT1	NM_022166.4	c.1730_1733dupATGA	p.Asp578GlufsTer2	frameshift_variant, stop_gained	Exon 8 of 12	ENST00000261381.7	NP_071449.1
XYLT1	XM_047434458.1	c.1691_1694dupATGA	p.Asp565GlufsTer2	frameshift_variant, stop_gained	Exon 7 of 11		XP_047290414.1
XYLT1	XM_017023539.3	c.1730_1733dupATGA	p.Asp578GlufsTer2	frameshift_variant, stop_gained	Exon 8 of 12		XP_016879028.1
LOC102723692	NR_135179.1	n.292_295dupCATT		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7	c.1730_1733dupATGA	p.Asp578GlufsTer2	frameshift_variant, stop_gained	Exon 8 of 12	1	NM_022166.4	ENSP00000261381.6
ENSG00000261448	ENST00000567344.1	n.292_295dupCATT		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Desbuquois dysplasia 2 Pathogenic:1

Feb 28, 2019

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided Pathogenic:1

Mar 21, 2024

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30554721) -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1085307563; hg19: chr16-17232242;