Variant 12-42087943-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_173601.2(GXYLT1):c.1166C>G(p.Ser389Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000337 in 1,483,592 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

GXYLT1
NM_173601.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.63

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]

GXYLT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2987367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GXYLT1	NM_173601.2 linkuse as main transcript	c.1166C>G	p.Ser389Cys	missense_variant	8/8	ENST00000398675.8
GXYLT1	NM_001099650.2 linkuse as main transcript	c.1073C>G	p.Ser358Cys	missense_variant	7/7
GXYLT1	XM_017019211.1 linkuse as main transcript	c.821C>G	p.Ser274Cys	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GXYLT1	ENST00000398675.8 linkuse as main transcript	c.1166C>G	p.Ser389Cys	missense_variant	8/8	1	NM_173601.2	P4	Q4G148-1
GXYLT1	ENST00000280876.6 linkuse as main transcript	c.1073C>G	p.Ser358Cys	missense_variant	7/7	1		A1	Q4G148-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.00000525

AC:

AN:

190492

Hom.:

AF XY:

0.00000945

AC XY:

AN XY:

105826

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000150

AC:

AN:

1331532

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

662760

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000389

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.66e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.00000829

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.1166C>G (p.S389C) alteration is located in exon 8 (coding exon 8) of the GXYLT1 gene. This alteration results from a C to G substitution at nucleotide position 1166, causing the serine (S) at amino acid position 389 to be replaced by a cysteine (C). 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

0.15

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Benign

0.23

T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.94

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.022

D;D

Sift4G

Uncertain

0.035

D;D

Polyphen

0.99

D;D

Vest4

0.47

MutPred

0.38

Loss of disorder (P = 0.0316);.;

MVP

0.10

MPC

0.69

ClinPred

0.93

GERP RS

3.7

Varity_R

0.14

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over