chr17-50346155-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1

The NM_022167.4(XYLT2):​c.15G>A​(p.Ala5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000664 in 1,267,174 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00066 ( 0 hom. )

Consequence

XYLT2
NM_022167.4 synonymous

Scores

1
1

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0200
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 17-50346155-G-A is Benign according to our data. Variant chr17-50346155-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1664871.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.02 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000656 (97/147922) while in subpopulation NFE AF= 0.00128 (85/66352). AF 95% confidence interval is 0.00106. There are 1 homozygotes in gnomad4. There are 42 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XYLT2NM_022167.4 linkuse as main transcriptc.15G>A p.Ala5= synonymous_variant 1/11 ENST00000017003.7
XYLT2NR_110010.2 linkuse as main transcriptn.30G>A non_coding_transcript_exon_variant 1/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XYLT2ENST00000017003.7 linkuse as main transcriptc.15G>A p.Ala5= synonymous_variant 1/111 NM_022167.4 P1Q9H1B5-1
XYLT2ENST00000376550.7 linkuse as main transcriptc.15G>A p.Ala5= synonymous_variant, NMD_transcript_variant 1/101
XYLT2ENST00000507602.5 linkuse as main transcriptc.15G>A p.Ala5= synonymous_variant 1/102
XYLT2ENST00000509778.1 linkuse as main transcriptc.15G>A p.Ala5= synonymous_variant 1/23

Frequencies

GnomAD3 genomes
AF:
0.000656
AC:
97
AN:
147922
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000244
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000672
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00100
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00128
Gnomad OTH
AF:
0.000490
GnomAD3 exomes
AF:
0.000428
AC:
34
AN:
79514
Hom.:
0
AF XY:
0.000354
AC XY:
16
AN XY:
45242
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000746
Gnomad ASJ exome
AF:
0.000151
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000482
Gnomad NFE exome
AF:
0.000946
Gnomad OTH exome
AF:
0.000459
GnomAD4 exome
AF:
0.000665
AC:
744
AN:
1119252
Hom.:
0
Cov.:
30
AF XY:
0.000650
AC XY:
358
AN XY:
551014
show subpopulations
Gnomad4 AFR exome
AF:
0.000139
Gnomad4 AMR exome
AF:
0.0000520
Gnomad4 ASJ exome
AF:
0.0000629
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00131
Gnomad4 NFE exome
AF:
0.000754
Gnomad4 OTH exome
AF:
0.000321
GnomAD4 genome
AF:
0.000656
AC:
97
AN:
147922
Hom.:
1
Cov.:
32
AF XY:
0.000583
AC XY:
42
AN XY:
72014
show subpopulations
Gnomad4 AFR
AF:
0.0000244
Gnomad4 AMR
AF:
0.0000672
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00100
Gnomad4 NFE
AF:
0.00128
Gnomad4 OTH
AF:
0.000490
Alfa
AF:
0.00105
Hom.:
0
Bravo
AF:
0.000518

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
CADD
Benign
15
DANN
Uncertain
0.97
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

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: rs376440990; hg19: chr17-48423516; API