17-50353652-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting

The NM_022167.4(XYLT2):​c.158G>A​(p.Arg53Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00003 in 1,565,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

XYLT2
NM_022167.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00
Variant links:
Genes affected
XYLT2 (HGNC:15517): (xylosyltransferase 2) The protein encoded by this gene is an isoform of xylosyltransferase, which belongs to a family of glycosyltransferases. This enzyme transfers xylose from UDP-xylose to specific serine residues of the core protein and initiates the biosynthesis of glycosaminoglycan chains in proteoglycans including chondroitin sulfate, heparan sulfate, heparin and dermatan sulfate. The enzyme activity, which is increased in scleroderma patients, is a diagnostic marker for the determination of sclerotic activity in systemic sclerosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08362445).
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000526 (8/152184) while in subpopulation EAS AF= 0.000964 (5/5186). AF 95% confidence interval is 0.00038. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
XYLT2NM_022167.4 linkuse as main transcriptc.158G>A p.Arg53Gln missense_variant 2/11 ENST00000017003.7 NP_071450.2 Q9H1B5-1B4DT06
XYLT2XM_005257572.5 linkuse as main transcriptc.62G>A p.Arg21Gln missense_variant 2/11 XP_005257629.1
XYLT2XM_047436522.1 linkuse as main transcriptc.-434G>A 5_prime_UTR_variant 2/11 XP_047292478.1
XYLT2NR_110010.2 linkuse as main transcriptn.173G>A non_coding_transcript_exon_variant 2/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
XYLT2ENST00000017003.7 linkuse as main transcriptc.158G>A p.Arg53Gln missense_variant 2/111 NM_022167.4 ENSP00000017003.2 Q9H1B5-1
XYLT2ENST00000376550.7 linkuse as main transcriptn.158G>A non_coding_transcript_exon_variant 2/101 ENSP00000365733.3 A0A0C4DFW8
XYLT2ENST00000507602.5 linkuse as main transcriptc.158G>A p.Arg53Gln missense_variant 2/102 ENSP00000426501.1 B4DT06
XYLT2ENST00000509778.1 linkuse as main transcriptc.113G>A p.Arg38Gln missense_variant 2/23 ENSP00000425511.1 D6RCT0

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152184
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000964
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:
0.0000516
AC:
9
AN:
174258
Hom.:
0
AF XY:
0.0000537
AC XY:
5
AN XY:
93172
show subpopulations
Gnomad AFR exome
AF:
0.0000984
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000226
Gnomad SAS exome
AF:
0.000208
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000276
AC:
39
AN:
1413734
Hom.:
0
Cov.:
31
AF XY:
0.0000258
AC XY:
18
AN XY:
698822
show subpopulations
Gnomad4 AFR exome
AF:
0.0000619
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000350
Gnomad4 SAS exome
AF:
0.000161
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000921
Gnomad4 OTH exome
AF:
0.0000171
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152184
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000964
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000336
AC:
4

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 15, 2023The c.158G>A (p.R53Q) alteration is located in exon 2 (coding exon 2) of the XYLT2 gene. This alteration results from a G to A substitution at nucleotide position 158, causing the arginine (R) at amino acid position 53 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.069
T;.;.
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.056
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.84
T;D;T
M_CAP
Benign
0.045
D
MetaRNN
Benign
0.084
T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.41
N;.;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-1.5
N;D;N
REVEL
Benign
0.050
Sift
Benign
0.21
T;T;T
Sift4G
Benign
0.22
T;T;T
Polyphen
0.059
B;.;.
Vest4
0.26
MutPred
0.16
Gain of methylation at K51 (P = 0.0715);.;Gain of methylation at K51 (P = 0.0715);
MVP
0.33
MPC
0.48
ClinPred
0.048
T
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.064
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs756927756; hg19: chr17-48431013; COSMIC: COSV99191078; COSMIC: COSV99191078; API