3-72888279-G-C

Variant names:

• chr3-72888279-G-C
• rs978834366
• NM_001080393.2:c.46G>C

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.46G>C​(p.Ala16Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000236 in 848,392 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. A16V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: GXYLT2 NM_001080393.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925
• 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=0.14627159).

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.46G>C	p.Ala16Pro	missense	Exon 1 of 7	NP_001073862.1	A0PJZ3
	GXYLT2	NR_138564.2		n.234G>C		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.46G>C	p.Ala16Pro	missense	Exon 1 of 7	ENSP00000374268.4	A0PJZ3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000236 AC: 2 AN: 848392 Hom.: 0 Cov.: 30 AF XY: 0.00000253 AC XY: 1 AN XY: 395248

African (AFR) AF: 0.00 AC: 0 AN: 15980

American (AMR) AF: 0.00 AC: 0 AN: 1530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5384

East Asian (EAS) AF: 0.00 AC: 0 AN: 4096

South Asian (SAS) AF: 0.00 AC: 0 AN: 18186

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1670

European-Non Finnish (NFE) AF: 0.00000259 AC: 2 AN: 772888

Other (OTH) AF: 0.00 AC: 0 AN: 27852

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.93
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.23
Sift	Benign	0.11	T
Sift4G	Benign	0.24	T
Polyphen		0.17	B
Vest4		0.46
MutPred		0.42		Loss of MoRF binding (P = 0.0691)
MVP		0.49
MPC		0.27
ClinPred		0.20	T
GERP RS		2.4
PromoterAI		-0.070	Neutral
Varity_R		0.12
gMVP		0.64
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: rs978834366; hg19: chr3-72937430;