3-72888248-C-G

Variant names:

• chr3-72888248-C-G
• rs1709103156
• NM_001080393.2:c.15C>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.15C>G​(p.Ser5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000401 in 847,780 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S5G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: GXYLT2 NM_001080393.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0640
• 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=0.098328084).

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.15C>G	p.Ser5Arg	missense	Exon 1 of 7	NP_001073862.1	A0PJZ3
	GXYLT2	NR_138564.2		n.203C>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.15C>G	p.Ser5Arg	missense	Exon 1 of 7	ENSP00000374268.4	A0PJZ3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000401 AC: 34 AN: 847780 Hom.: 0 Cov.: 30 AF XY: 0.0000481 AC XY: 19 AN XY: 394822

African (AFR) AF: 0.00 AC: 0 AN: 15966

American (AMR) AF: 0.00 AC: 0 AN: 1282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5318

East Asian (EAS) AF: 0.00 AC: 0 AN: 4114

South Asian (SAS) AF: 0.000168 AC: 3 AN: 17840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1660

European-Non Finnish (NFE) AF: 0.0000401 AC: 31 AN: 772956

Other (OTH) AF: 0.00 AC: 0 AN: 27838

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.064
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.54	N
REVEL	Benign	0.031
Sift	Benign	0.10	T
Sift4G	Benign	0.45	T
Polyphen		0.028	B
Vest4		0.39
MutPred		0.28		Gain of glycosylation at S5 (P = 0.0135)
MVP		0.32
MPC		0.24
ClinPred		0.12	T
GERP RS		0.34
PromoterAI		0.067	Neutral
Varity_R		0.13
gMVP		0.51
Mutation Taster		=79/21	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: rs1709103156; hg19: chr3-72937399;