3-72961770-A-T

Position:

• chr3-72961770-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080393.2(GXYLT2):​c.976+4418A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 151,642 control chromosomes in the GnomAD database, including 32,051 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (32051 hom., cov: 30)
• Consequence: GXYLT2 NM_001080393.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GXYLT2	NM_001080393.2	c.976+4418A>T		intron_variant		ENST00000389617.9	NP_001073862.1
GXYLT2	NR_138564.2	n.1159+4418A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GXYLT2	ENST00000389617.9	c.976+4418A>T		intron_variant		5	NM_001080393.2	ENSP00000374268	P1
GXYLT2	ENST00000491839.1	c.259+4418A>T		intron_variant		3		ENSP00000420426

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97479 AN: 151526 Hom.: 32042 Cov.: 30

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.643

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.643 AC: 97526 AN: 151642 Hom.: 32051 Cov.: 30 AF XY: 0.647 AC XY: 47885 AN XY: 74058

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.642

Alfa AF: 0.661 Hom.: 4178

Bravo AF: 0.639

Asia WGS AF: 0.589 AC: 2046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs1388276; hg19: chr3-73010921;