3-72888378-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080393.2(GXYLT2):​c.145C>T​(p.Pro49Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000203 in 985,866 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. P49L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: GXYLT2 NM_001080393.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06376019).

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>T	p.Pro49Ser	missense	Exon 1 of 7	NP_001073862.1	A0PJZ3
	GXYLT2	NR_138564.2		n.333C>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.145C>T	p.Pro49Ser	missense	Exon 1 of 7	ENSP00000374268.4	A0PJZ3

Frequencies

GnomAD3 genomes AF: 0.00000684 AC: 1 AN: 146122 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000119 AC: 1 AN: 839744 Hom.: 0 Cov.: 30 AF XY: 0.00000257 AC XY: 1 AN XY: 388498

African (AFR) AF: 0.00 AC: 0 AN: 15878

American (AMR) AF: 0.00 AC: 0 AN: 1226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5292

East Asian (EAS) AF: 0.000262 AC: 1 AN: 3818

South Asian (SAS) AF: 0.00 AC: 0 AN: 17148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1646

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 766216

Other (OTH) AF: 0.00 AC: 0 AN: 27688

GnomAD4 genome AF: 0.00000684 AC: 1 AN: 146122 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 71058

African (AFR) AF: 0.00 AC: 0 AN: 40798

American (AMR) AF: 0.00 AC: 0 AN: 14750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.000199 AC: 1 AN: 5020

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65772

Other (OTH) AF: 0.00 AC: 0 AN: 2018

Alfa AF: 0.00 Hom.: 0

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	0.075
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.2
DANN	Benign	0.93
DEOGEN2	Benign	0.00087	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.0050
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.19	N
REVEL	Benign	0.032
Sift	Uncertain	0.014	D
Sift4G	Benign	0.44	T
Polyphen		0.0010	B
Vest4		0.085
MutPred		0.21		Gain of MoRF binding (P = 0.0296)
MVP		0.21
MPC		0.15
ClinPred		0.086	T
GERP RS		0.20
PromoterAI		-0.021	Neutral
Varity_R		0.054
gMVP		0.44
Mutation Taster		=90/10	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;