Genetic Variant NM_001080393.2:c.164C>A (chr3-72888397-C-A) – 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>A(p.Pro55Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000117 in 853,230 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: not found (cov: 30)

Exomes 𝑓: 0.0000012 ( 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:

Genome browser will be placed here

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=0.106514424).

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>A	p.Pro55Gln	missense	Exon 1 of 7	NP_001073862.1	A0PJZ3
	GXYLT2	NR_138564.2		n.352C>A		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>A	p.Pro55Gln	missense	Exon 1 of 7	ENSP00000374268.4	A0PJZ3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000117

AC:

AN:

853230

Hom.:

Cov.:

AF XY:

0.00000253

AC XY:

AN XY:

395938

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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:

0.0000579

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:

0.00

AC:

AN:

775308

Other (OTH)

AF:

0.00

AC:

AN:

28560

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0020

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.35

M_CAP

Benign

0.016

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

0.31

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.24

REVEL

Benign

0.030

Sift

Benign

0.34

Sift4G

Benign

0.32

Polyphen

0.82

Vest4

0.16

MutPred

0.22

Gain of MoRF binding (P = 0.0384)

MVP

0.33

MPC

0.14

ClinPred

0.14

GERP RS

1.3

PromoterAI

-0.098

Neutral

(source)

Varity_R

0.047

gMVP

0.57

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over