rs2303393

Positions:

• chr2-165749290-A-G
• chr2-165749290-A-T

Variant summary

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

The NM_004482.4(GALNT3):​c.1780-387T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,966 control chromosomes in the GnomAD database, including 12,981 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 0.39 (12981 hom., cov: 32)
• Consequence: GALNT3 NM_004482.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

Genes affected

GALNT3 (HGNC:4125): (polypeptide N-acetylgalactosaminyltransferase 3) This gene encodes UDP-GalNAc transferase 3, a member of the GalNAc-transferases family. This family transfers an N-acetyl galactosamine to the hydroxyl group of a serine or threonine residue in the first step of O-linked oligosaccharide biosynthesis. Individual GalNAc-transferases have distinct activities and initiation of O-glycosylation is regulated by a repertoire of GalNAc-transferases. The protein encoded by this gene is highly homologous to other family members, however the enzymes have different substrate specificities. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT3	NM_004482.4	c.1780-387T>C		intron_variant		ENST00000392701.8
GALNT3	XM_005246449.2	c.1780-387T>C		intron_variant
GALNT3	XM_011510929.2	c.1780-387T>C		intron_variant
GALNT3	XM_017003770.2	c.1780-387T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT3	ENST00000392701.8	c.1780-387T>C		intron_variant		1	NM_004482.4	P1
GALNT3	ENST00000409882.5	c.994-387T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59529 AN: 151846 Hom.: 12972 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.392 AC: 59555 AN: 151966 Hom.: 12981 Cov.: 32 AF XY: 0.393 AC XY: 29160 AN XY: 74278

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.397

Alfa AF: 0.435 Hom.: 2395

Bravo AF: 0.370

Asia WGS AF: 0.345 AC: 1196 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.014
DANN	Benign	0.49

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: rs2303393; hg19: chr2-166605800;