Variant 16-17259071-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_022166.4(XYLT1):c.830G>A(p.Arg277His) variant causes a missense change. The variant allele was found at a frequency of 0.00000983 in 1,526,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

XYLT1
NM_022166.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.07

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]

XYLT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
XYLT1	NM_022166.4 linkuse as main transcript	c.830G>A	p.Arg277His	missense_variant	3/12	ENST00000261381.7	NP_071449.1
XYLT1	XM_047434458.1 linkuse as main transcript	c.791G>A	p.Arg264His	missense_variant	2/11		XP_047290414.1
XYLT1	XM_017023539.3 linkuse as main transcript	c.830G>A	p.Arg277His	missense_variant	3/12		XP_016879028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XYLT1	ENST00000261381.7 linkuse as main transcript	c.830G>A	p.Arg277His	missense_variant	3/12	1	NM_022166.4	ENSP00000261381	P1
XYLT1	ENST00000575674.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000214

AC:

AN:

187170

Hom.:

AF XY:

0.0000101

AC XY:

AN XY:

99100

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000137

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000624

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000102

AC:

AN:

1374146

Hom.:

Cov.:

AF XY:

0.00000890

AC XY:

AN XY:

674008

show subpopulations

Gnomad4 AFR exome

AF:

0.0000659

Gnomad4 AMR exome

AF:

0.000132

Gnomad4 ASJ exome

AF:

0.0000485

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.0000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000374

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151956

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.84

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.34

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.79

MutPred

0.42

Loss of MoRF binding (P = 0.0084);

MVP

0.22

MPC

0.92

ClinPred

0.90

GERP RS

5.4

Varity_R

0.59

gMVP

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over