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GeneBe

12-42109665-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_173601.2(GXYLT1):c.513A>G(p.Thr171=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,537,008 control chromosomes in the GnomAD database, including 108,986 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.34 ( 9278 hom., cov: 31)
Exomes 𝑓: 0.37 ( 99708 hom. )

Consequence

GXYLT1
NM_173601.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.23
Variant links:
Genes affected
GXYLT1 (HGNC:27482): (glucoside xylosyltransferase 1) GXYLT1 is a xylosyltransferase (EC 2.4.2.-) that adds the first xylose to O-glucose-modified residues in the epidermal growth factor (EGF; MIM 131530) repeats of proteins such as NOTCH1 (MIM 190198) (Sethi et al., 2010 [PubMed 19940119]).[supplied by OMIM, Mar 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-42109665-T-C is Benign according to our data. Variant chr12-42109665-T-C is described in ClinVar as [Benign]. Clinvar id is 3059349.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.23 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GXYLT1NM_173601.2 linkuse as main transcriptc.513A>G p.Thr171= synonymous_variant 4/8 ENST00000398675.8
GXYLT1NM_001099650.2 linkuse as main transcriptc.420A>G p.Thr140= synonymous_variant 3/7
GXYLT1XM_017019211.1 linkuse as main transcriptc.168A>G p.Thr56= synonymous_variant 4/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GXYLT1ENST00000398675.8 linkuse as main transcriptc.513A>G p.Thr171= synonymous_variant 4/81 NM_173601.2 P4Q4G148-1
GXYLT1ENST00000280876.6 linkuse as main transcriptc.420A>G p.Thr140= synonymous_variant 3/71 A1Q4G148-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.340
AC:
51625
AN:
151730
Hom.:
9277
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.237
Gnomad AMI
AF:
0.500
Gnomad AMR
AF:
0.303
Gnomad ASJ
AF:
0.361
Gnomad EAS
AF:
0.403
Gnomad SAS
AF:
0.489
Gnomad FIN
AF:
0.448
Gnomad MID
AF:
0.361
Gnomad NFE
AF:
0.377
Gnomad OTH
AF:
0.332
GnomAD3 exomes
AF:
0.373
AC:
81828
AN:
219170
Hom.:
15969
AF XY:
0.383
AC XY:
45734
AN XY:
119452
show subpopulations
Gnomad AFR exome
AF:
0.230
Gnomad AMR exome
AF:
0.261
Gnomad ASJ exome
AF:
0.361
Gnomad EAS exome
AF:
0.392
Gnomad SAS exome
AF:
0.496
Gnomad FIN exome
AF:
0.442
Gnomad NFE exome
AF:
0.377
Gnomad OTH exome
AF:
0.369
GnomAD4 exome
AF:
0.375
AC:
519201
AN:
1385160
Hom.:
99708
Cov.:
27
AF XY:
0.380
AC XY:
262160
AN XY:
690598
show subpopulations
Gnomad4 AFR exome
AF:
0.223
Gnomad4 AMR exome
AF:
0.269
Gnomad4 ASJ exome
AF:
0.358
Gnomad4 EAS exome
AF:
0.395
Gnomad4 SAS exome
AF:
0.496
Gnomad4 FIN exome
AF:
0.432
Gnomad4 NFE exome
AF:
0.371
Gnomad4 OTH exome
AF:
0.372
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.340
AC:
51641
AN:
151848
Hom.:
9278
Cov.:
31
AF XY:
0.348
AC XY:
25837
AN XY:
74230
show subpopulations
Gnomad4 AFR
AF:
0.237
Gnomad4 AMR
AF:
0.303
Gnomad4 ASJ
AF:
0.361
Gnomad4 EAS
AF:
0.402
Gnomad4 SAS
AF:
0.490
Gnomad4 FIN
AF:
0.448
Gnomad4 NFE
AF:
0.377
Gnomad4 OTH
AF:
0.332
Alfa
AF:
0.357
Hom.:
3389
Bravo
AF:
0.319
Asia WGS
AF:
0.421
AC:
1452
AN:
3462

ClinVar

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

Submissions by phenotype

GXYLT1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 30, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
Cadd
Benign
7.9
Dann
Benign
0.69

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.

Other links and lift over

dbSNP: rs7312933; hg19: chr12-42503467; COSMIC: COSV55136854; API