Genetic Variant GXYLT2:p.Pro39Ser (chr3-72888348-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080393.2(GXYLT2):c.115C>T(p.Pro39Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 145,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GXYLT2
NM_001080393.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0330

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0651969).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080393.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GXYLT2	NM_001080393.2	MANE Select	c.115C>T	p.Pro39Ser	missense	Exon 1 of 7	NP_001073862.1	A0PJZ3
	GXYLT2	NR_138564.2		n.303C>T		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GXYLT2	ENST00000389617.9	TSL:5 MANE Select	c.115C>T	p.Pro39Ser	missense	Exon 1 of 7	ENSP00000374268.4	A0PJZ3

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

145920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000490

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

836922

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

387218

African (AFR)

AF:

0.00

AC:

AN:

15802

American (AMR)

AF:

0.00

AC:

AN:

1112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5228

East Asian (EAS)

AF:

0.00

AC:

AN:

3736

South Asian (SAS)

AF:

0.00

AC:

AN:

17246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1634

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

764232

Other (OTH)

AF:

0.00

AC:

AN:

27484

GnomAD4 genome

AF:

0.0000137

AC:

AN:

145920

Hom.:

Cov.:

AF XY:

0.0000282

AC XY:

AN XY:

70944

show subpopulations

African (AFR)

AF:

0.0000490

AC:

AN:

40788

American (AMR)

AF:

0.00

AC:

AN:

14712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3388

East Asian (EAS)

AF:

0.00

AC:

AN:

5016

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65690

Other (OTH)

AF:

0.00

AC:

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0013

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.42

M_CAP

Benign

0.014

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.033

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.21

REVEL

Benign

0.028

Sift

Benign

0.27

Sift4G

Benign

0.94

Polyphen

0.20

Vest4

0.073

MutPred

0.16

Loss of glycosylation at P36 (P = 0.0171)

MVP

0.20

MPC

0.15

ClinPred

0.087

GERP RS

1.3

PromoterAI

-0.053

Neutral

(source)

Varity_R

0.050

gMVP

0.46

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over