3-72996500-T-C

Variant names:

• chr3-72996500-T-C
• rs9816164
• ENST00000491839.1:c.433-1577T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000491839.1(GXYLT2):​c.433-1577T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,156 control chromosomes in the GnomAD database, including 24,060 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 0.56 (24060 hom., cov: 33)
• Consequence: GXYLT2 ENST00000491839.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 10 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]

ENSG00000310267 (HGNC:):

PPP4R2 (HGNC:18296): (protein phosphatase 4 regulatory subunit 2) The protein encoded by this gene is a regulatory subunit of the serine/threonine-protein phosphatase 4 complex. In addition to being required for efficient DNA double strand break repair, this complex plays a role in organization of microtubules at centrosomes and processing of spliceosomal snRNPs. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000491839.1. 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
	PPP4R2	NM_001318026.2		c.-381T>C		upstream_gene	N/A	NP_001304955.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GXYLT2	ENST00000491839.1	TSL:3	c.433-1577T>C		intron	N/A	ENSP00000420426.1	C9JND4
	ENSG00000310267	ENST00000848625.1		n.131+607A>G		intron	N/A
	ENSG00000310267	ENST00000848626.1		n.352+310A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84721 AN: 152038 Hom.: 24045 Cov.: 33

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.557 AC: 84773 AN: 152156 Hom.: 24060 Cov.: 33 AF XY: 0.552 AC XY: 41020 AN XY: 74356

African (AFR) AF: 0.661 AC: 27450 AN: 41540

American (AMR) AF: 0.447 AC: 6833 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1742 AN: 3470

East Asian (EAS) AF: 0.440 AC: 2271 AN: 5160

South Asian (SAS) AF: 0.628 AC: 3027 AN: 4820

European-Finnish (FIN) AF: 0.516 AC: 5456 AN: 10572

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36348 AN: 67974

Other (OTH) AF: 0.539 AC: 1141 AN: 2116

Alfa AF: 0.557 Hom.: 3471

Bravo AF: 0.548

Asia WGS AF: 0.556 AC: 1933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.52
PhyloP100		-0.12
PromoterAI		0.0044	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9816164; hg19: chr3-73045651;