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GeneBe

16-17108697-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022166.4(XYLT1):c.2878T>C(p.Ter960GlnextTer44) variant causes a stop lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

XYLT1
NM_022166.4 stop_lost

Scores

2
1
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.09
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_addAF=-0.228517).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XYLT1NM_022166.4 linkuse as main transcriptc.2878T>C p.Ter960GlnextTer44 stop_lost 12/12 ENST00000261381.7
XYLT1XM_047434458.1 linkuse as main transcriptc.2839T>C p.Ter947GlnextTer44 stop_lost 11/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XYLT1ENST00000261381.7 linkuse as main transcriptc.2878T>C p.Ter960GlnextTer44 stop_lost 12/121 NM_022166.4 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Desbuquois dysplasia 1 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeMay 07, 2022This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with XYLT1-related conditions. This sequence change disrupts the translational stop signal of the XYLT1 mRNA. It is expected to extend the length of the XYLT1 protein by 44 additional amino acid residues. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
Cadd
Benign
17
Dann
Benign
0.86
Eigen
Pathogenic
1.2
Eigen_PC
Pathogenic
1.0
FATHMM_MKL
Uncertain
0.95
D
MutationTaster
Benign
1.0
N
Vest4
0.011
GERP RS
5.4

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-17202554; API