Variant 12-42144469-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173601.2(GXYLT1):c.178G>T(p.Ala60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,297,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A60A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

GXYLT1
NM_173601.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0039165616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GXYLT1	NM_173601.2 linkuse as main transcript	c.178G>T	p.Ala60Ser	missense_variant	1/8	ENST00000398675.8
GXYLT1	NM_001099650.2 linkuse as main transcript	c.178G>T	p.Ala60Ser	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GXYLT1	ENST00000398675.8 linkuse as main transcript	c.178G>T	p.Ala60Ser	missense_variant	1/8	1	NM_173601.2	P4	Q4G148-1
GXYLT1	ENST00000280876.6 linkuse as main transcript	c.178G>T	p.Ala60Ser	missense_variant	1/7	1		A1	Q4G148-2

Frequencies

GnomAD3 genomes

AF:

0.0000409

AC:

AN:

146840

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000510

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000606

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000174

AC:

AN:

17228

Hom.:

AF XY:

0.000175

AC XY:

AN XY:

11456

show subpopulations

Gnomad AFR exome

AF:

0.00714

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:

0.000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1150696

Hom.:

Cov.:

AF XY:

0.0000302

AC XY:

AN XY:

562060

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000335

Gnomad4 OTH exome

AF:

0.0000215

GnomAD4 genome

AF:

0.0000409

AC:

AN:

146840

Hom.:

Cov.:

AF XY:

0.0000697

AC XY:

AN XY:

71758

show subpopulations

Gnomad4 AFR

AF:

0.0000510

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000606

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000511

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

May 24, 2023

The c.178G>T (p.A60S) alteration is located in exon 1 (coding exon 1) of the GXYLT1 gene. This alteration results from a G to T substitution at nucleotide position 178, causing the alanine (A) at amino acid position 60 to be replaced by a serine (S). 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

0.092

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.40

Cadd

Benign

8.5

Dann

Benign

0.82

DEOGEN2

Benign

0.010

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.16

N;N

REVEL

Benign

0.017

Sift

Benign

0.90

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.020

B;B

Vest4

0.091

MutPred

0.25

Gain of glycosylation at A60 (P = 3e-04);Gain of glycosylation at A60 (P = 3e-04);

MVP

0.043

MPC

0.20

ClinPred

0.011

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.036

gMVP

0.27

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.

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