dbSNP rs1457612277: XYLT1:p.Arg406Gln (chr16-17198284-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022166.4(XYLT1):c.1217G>A(p.Arg406Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R406W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

XYLT1
NM_022166.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Desbuquois dysplasia 2
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Desbuquois dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
XYLT1-congenital disorder of glycosylation
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

XYLT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1527802).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022166.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLT1	NM_022166.4	MANE Select	c.1217G>A	p.Arg406Gln	missense	Exon 5 of 12	NP_071449.1	Q86Y38

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XYLT1	ENST00000261381.7	TSL:1 MANE Select	c.1217G>A	p.Arg406Gln	missense	Exon 5 of 12	ENSP00000261381.6	Q86Y38
XYLT1	ENST00000933757.1		c.1217G>A	p.Arg406Gln	missense	Exon 5 of 12	ENSP00000603816.1
XYLT1	ENST00000575674.1	TSL:3	n.345G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251222

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1112000

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000192

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.608

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000487

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Desbuquois dysplasia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

Eigen

Benign

-0.042

Eigen_PC

Benign

0.070

FATHMM_MKL

Uncertain

0.77

M_CAP

Benign

0.0078

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

PhyloP100

1.2

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.56

REVEL

Benign

0.096

Sift

Benign

0.85

Sift4G

Benign

0.95

Polyphen

0.97

Vest4

0.19

MutPred

0.61

Loss of stability (P = 0.1567)

MVP

0.082

MPC

0.47

ClinPred

0.55

GERP RS

4.4

Varity_R

0.24

gMVP

0.45

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over