16-17470454-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022166.4(XYLT1):c.343G>C(p.Ala115Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000185 in 1,078,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A115S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: XYLT1 NM_022166.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397

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]

LOC107987234 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06917885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XYLT1	NM_022166.4	c.343G>C	p.Ala115Pro	missense_variant	1/12	ENST00000261381.7
XYLT1	XM_047434458.1	c.343G>C	p.Ala115Pro	missense_variant	1/11
XYLT1	XM_017023539.3	c.343G>C	p.Ala115Pro	missense_variant	1/12
LOC107987234	XR_001752091.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XYLT1	ENST00000261381.7	c.343G>C	p.Ala115Pro	missense_variant	1/12	1	NM_022166.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000185 AC: 2 AN: 1078704 Hom.: 0 Cov.: 30 AF XY: 0.00000392 AC XY: 2 AN XY: 510142

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000475

Gnomad4 NFE exome AF: 0.00000109

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.39	N
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.55	N
MutationTaster	Benign	0.69	N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.038
Sift	Benign	0.18	T
Sift4G	Benign	0.24	T
Polyphen		0.35	B
Vest4		0.047
MutPred		0.23		Gain of glycosylation at A115 (P = 0.0242);
MVP		0.043
MPC		0.30
ClinPred		0.29	T
GERP RS		1.8
Varity_R		0.11
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs61758388; hg19: chr16-17564311;