3-72888378-C-G

Variant names:

• chr3-72888378-C-G
• rs1263034397
• NM_001080393.2:c.145C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080393.2(GXYLT2):​c.145C>G​(p.Pro49Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P49L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GXYLT2 NM_001080393.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 0 publications found

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]

ACMG classification

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=0.06909552).

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.145C>G	p.Pro49Ala	missense	Exon 1 of 7	NP_001073862.1	A0PJZ3
	GXYLT2	NR_138564.2		n.333C>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.145C>G	p.Pro49Ala	missense	Exon 1 of 7	ENSP00000374268.4	A0PJZ3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.8
DANN	Benign	0.52
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.0050
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.17	N
REVEL	Benign	0.027
Sift	Uncertain	0.022	D
Sift4G	Benign	0.21	T
Polyphen		0.015	B
Vest4		0.12
MutPred		0.18		Loss of glycosylation at P47 (P = 0.0389)
MVP		0.21
MPC		0.15
ClinPred		0.079	T
GERP RS		0.20
PromoterAI		-0.075	Neutral
Varity_R		0.053
gMVP		0.38
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs1263034397; hg19: chr3-72937529;