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GeneBe

12-42097577-T-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_173601.2(GXYLT1):c.1026A>T(p.Arg342=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 1,607,582 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 7 hom., cov: 32)
Exomes 𝑓: 0.0069 ( 45 hom. )

Consequence

GXYLT1
NM_173601.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.53
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 -11 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=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-42097577-T-A is Benign according to our data. Variant chr12-42097577-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642888.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=-1.53 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 7 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GXYLT1NM_173601.2 linkuse as main transcriptc.1026A>T p.Arg342= synonymous_variant 7/8 ENST00000398675.8
GXYLT1NM_001099650.2 linkuse as main transcriptc.933A>T p.Arg311= synonymous_variant 6/7
GXYLT1XM_017019211.1 linkuse as main transcriptc.681A>T p.Arg227= synonymous_variant 7/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GXYLT1ENST00000398675.8 linkuse as main transcriptc.1026A>T p.Arg342= synonymous_variant 7/81 NM_173601.2 P4Q4G148-1
GXYLT1ENST00000280876.6 linkuse as main transcriptc.933A>T p.Arg311= synonymous_variant 6/71 A1Q4G148-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00576
AC:
876
AN:
152118
Hom.:
7
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00152
Gnomad AMI
AF:
0.0154
Gnomad AMR
AF:
0.00517
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.00669
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00927
Gnomad OTH
AF:
0.00526
GnomAD3 exomes
AF:
0.00508
AC:
1228
AN:
241702
Hom.:
7
AF XY:
0.00514
AC XY:
673
AN XY:
130932
show subpopulations
Gnomad AFR exome
AF:
0.00150
Gnomad AMR exome
AF:
0.00252
Gnomad ASJ exome
AF:
0.00112
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00221
Gnomad FIN exome
AF:
0.00477
Gnomad NFE exome
AF:
0.00829
Gnomad OTH exome
AF:
0.00473
GnomAD4 exome
AF:
0.00690
AC:
10044
AN:
1455346
Hom.:
45
Cov.:
30
AF XY:
0.00678
AC XY:
4909
AN XY:
723618
show subpopulations
Gnomad4 AFR exome
AF:
0.000935
Gnomad4 AMR exome
AF:
0.00237
Gnomad4 ASJ exome
AF:
0.00123
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00187
Gnomad4 FIN exome
AF:
0.00501
Gnomad4 NFE exome
AF:
0.00818
Gnomad4 OTH exome
AF:
0.00603
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00575
AC:
876
AN:
152236
Hom.:
7
Cov.:
32
AF XY:
0.00594
AC XY:
442
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.00152
Gnomad4 AMR
AF:
0.00517
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.00669
Gnomad4 NFE
AF:
0.00927
Gnomad4 OTH
AF:
0.00521
Alfa
AF:
0.00766
Hom.:
4
Bravo
AF:
0.00516
Asia WGS
AF:
0.000289
AC:
1
AN:
3474
EpiCase
AF:
0.00698
EpiControl
AF:
0.00748

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 testingCeGaT Center for Human Genetics TuebingenJun 01, 2022GXYLT1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
9.2
Dann
Benign
0.56
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: rs139072942; hg19: chr12-42491379; API