Variant chr3-72888280-C-T 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_001080393.2(GXYLT2):c.47C>T(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000118 in 848,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

GXYLT2
NM_001080393.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.63

Variant links:

Genes affected

GXYLT2 (HGNC:33383): (glucoside xylosyltransferase 2) The protein encoded by this gene is a xylosyltransferase that elongates O-linked glucose bound to epidermal growth factor (EGF) repeats. The encoded protein catalyzes the addition of xylose to the O-glucose-modified residues of EGF repeats of Notch proteins. [provided by RefSeq, Sep 2016]

GXYLT2 links:

GXYLT2 (HGNC:):

GXYLT2 links:

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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=0.053397924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GXYLT2	NM_001080393.2 linkuse as main transcript	c.47C>T	p.Ala16Val	missense_variant	1/7	ENST00000389617.9	NP_001073862.1	A0PJZ3
GXYLT2	NR_138564.2 linkuse as main transcript	n.235C>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GXYLT2	ENST00000389617.9 linkuse as main transcript	c.47C>T	p.Ala16Val	missense_variant	1/7	5	NM_001080393.2	ENSP00000374268.4		A0PJZ3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000118

AC:

AN:

848344

Hom.:

Cov.:

AF XY:

0.00000253

AC XY:

AN XY:

395246

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:

0.00000129

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 07, 2024

The c.47C>T (p.A16V) alteration is located in exon 1 (coding exon 1) of the GXYLT2 gene. This alteration results from a C to T substitution at nucleotide position 47, causing the alanine (A) at amino acid position 16 to be replaced by a valine (V). 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

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0057

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.34

M_CAP

Benign

0.018

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.15

REVEL

Benign

0.029

Sift

Benign

1.0

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.19

MutPred

0.38

Gain of catalytic residue at A16 (P = 0.078);

MVP

0.30

MPC

0.22

ClinPred

0.16

GERP RS

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.030

gMVP

0.51

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over