NM_001080393.2:c.46G>T

Variant names:

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

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>T​(p.Ala16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 994,556 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. A16V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: GXYLT2 NM_001080393.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.081590176).

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>T	p.Ala16Ser	missense	Exon 1 of 7	NP_001073862.1	A0PJZ3
	GXYLT2	NR_138564.2		n.234G>T		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>T	p.Ala16Ser	missense	Exon 1 of 7	ENSP00000374268.4	A0PJZ3

Frequencies

GnomAD3 genomes AF: 0.0000205 AC: 3 AN: 146164 Hom.: 0 Cov.: 30

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: 0.000119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000304

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000530 AC: 45 AN: 848392 Hom.: 0 Cov.: 30 AF XY: 0.0000557 AC XY: 22 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: 0.00124 AC: 1 AN: 806

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

European-Non Finnish (NFE) AF: 0.0000569 AC: 44 AN: 772888

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

GnomAD4 genome AF: 0.0000205 AC: 3 AN: 146164 Hom.: 0 Cov.: 30 AF XY: 0.0000422 AC XY: 3 AN XY: 71054

African (AFR) AF: 0.00 AC: 0 AN: 40834

American (AMR) AF: 0.00 AC: 0 AN: 14736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 5020

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.000119 AC: 1 AN: 8374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000304 AC: 2 AN: 65754

Other (OTH) AF: 0.00 AC: 0 AN: 2020

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

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	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.6
DANN	Benign	0.97
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.93
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.064
Sift	Benign	0.15	T
Sift4G	Benign	0.49	T
Polyphen		0.0060	B
Vest4		0.17
MutPred		0.29		Gain of MoRF binding (P = 0.1155)
MVP		0.36
MPC		0.20
ClinPred		0.18	T
GERP RS		2.4
PromoterAI		-0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.046
gMVP		0.56
Mutation Taster		=91/9	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;