NM_001080393.2:c.164C>T

Variant names:

• chr3-72888397-C-T
• rs1462412316
• NM_001080393.2:c.164C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001080393.2(GXYLT2):​c.164C>T​(p.Pro55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000703 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: GXYLT2 NM_001080393.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.306
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08284286).

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>T	p.Pro55Leu	missense	Exon 1 of 7	NP_001073862.1	A0PJZ3
	GXYLT2	NR_138564.2		n.352C>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.164C>T	p.Pro55Leu	missense	Exon 1 of 7	ENSP00000374268.4	A0PJZ3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000703 AC: 6 AN: 853230 Hom.: 0 Cov.: 30 AF XY: 0.00000758 AC XY: 3 AN XY: 395938

African (AFR) AF: 0.00 AC: 0 AN: 16236

American (AMR) AF: 0.00 AC: 0 AN: 1652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5638

East Asian (EAS) AF: 0.00 AC: 0 AN: 4580

South Asian (SAS) AF: 0.000289 AC: 5 AN: 17284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 775308

Other (OTH) AF: 0.0000350 AC: 1 AN: 28560

GnomAD4 genome Cov.: 30

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	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.00085	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.31
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.25	N
REVEL	Benign	0.060
Sift	Benign	0.056	T
Sift4G	Benign	0.11	T
Polyphen		0.0020	B
Vest4		0.20
MutPred		0.26		Gain of MoRF binding (P = 0.0234)
MVP		0.33
MPC		0.15
ClinPred		0.16	T
GERP RS		1.3
PromoterAI		-0.055	Neutral
Varity_R		0.039
gMVP		0.52
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: rs1462412316; hg19: chr3-72937548;