Genetic Variant GXYLT2:p.Pro55Arg (chr3-72888397-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080393.2(GXYLT2):c.164C>G(p.Pro55Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000043 in 999,722 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P55L) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

GXYLT2
NM_001080393.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.306

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1152598).

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.164C>G	p.Pro55Arg	missense	Exon 1 of 7	NP_001073862.1	A0PJZ3
	GXYLT2	NR_138564.2		n.352C>G		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.164C>G	p.Pro55Arg	missense	Exon 1 of 7	ENSP00000374268.4	A0PJZ3

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

146492

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000303

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000481

AC:

AN:

853230

Hom.:

Cov.:

AF XY:

0.0000631

AC XY:

AN XY:

395938

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16236

American (AMR)

AF:

0.00

AC:

AN:

1652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5638

East Asian (EAS)

AF:

0.00

AC:

AN:

4580

South Asian (SAS)

AF:

0.00

AC:

AN:

17284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1714

European-Non Finnish (NFE)

AF:

0.0000529

AC:

AN:

775308

Other (OTH)

AF:

0.00

AC:

AN:

28560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000137

AC:

AN:

146492

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

71262

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40808

American (AMR)

AF:

0.00

AC:

AN:

14794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3396

East Asian (EAS)

AF:

0.00

AC:

AN:

4996

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000303

AC:

AN:

65996

Other (OTH)

AF:

0.00

AC:

AN:

2020

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:

0.000142

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0020

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.38

M_CAP

Benign

0.015

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

0.31

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.36

REVEL

Benign

0.023

Sift

Benign

0.10

Sift4G

Benign

0.18

Polyphen

0.69

Vest4

0.19

MutPred

0.33

Gain of MoRF binding (P = 0.0027)

MVP

0.38

MPC

0.16

ClinPred

0.16

GERP RS

1.3

PromoterAI

-0.072

Neutral

(source)

Varity_R

0.034

gMVP

0.59

Mutation Taster

=90/10

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over