NM_004482.4:c.1780-387T>C

Variant names:

• chr2-165749290-A-G
• rs2303393
• NM_004482.4:c.1780-387T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

GALNT3 Gene-Disease associations (from GenCC):

• tumoral calcinosis, hyperphosphatemic, familial, 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• tumoral calcinosis, hyperphosphatemic, familial, 1

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia

ENSG00000307262 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GALNT3	NM_004482.4	c.1780-387T>C		intron_variant	Intron 10 of 10	ENST00000392701.8	NP_004473.2
GALNT3	XM_005246449.2	c.1780-387T>C		intron_variant	Intron 10 of 10		XP_005246506.1
GALNT3	XM_011510929.2	c.1780-387T>C		intron_variant	Intron 10 of 10		XP_011509231.1
GALNT3	XM_017003770.2	c.1780-387T>C		intron_variant	Intron 10 of 10		XP_016859259.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT3	ENST00000392701.8	c.1780-387T>C		intron_variant	Intron 10 of 10	1	NM_004482.4	ENSP00000376465.3
GALNT3	ENST00000409882.5	c.994-387T>C		intron_variant	Intron 7 of 7	1		ENSP00000386955.1
GALNT3	ENST00000715282.1	c.1780-387T>C		intron_variant	Intron 10 of 10			ENSP00000520447.1
ENSG00000307262	ENST00000824811.1	n.131-507A>G		intron_variant	Intron 1 of 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

African (AFR) AF: 0.207 AC: 8569 AN: 41480

American (AMR) AF: 0.349 AC: 5323 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1740 AN: 3464

East Asian (EAS) AF: 0.354 AC: 1831 AN: 5168

South Asian (SAS) AF: 0.365 AC: 1758 AN: 4816

European-Finnish (FIN) AF: 0.484 AC: 5121 AN: 10572

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33728 AN: 67898

Other (OTH) AF: 0.397 AC: 838 AN: 2110

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
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs2303393; hg19: chr2-166605800;