rs13429321

Variant names:

• chr2-165748500-A-T
• rs13429321
• NM_004482.4:c.*281T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004482.4(GALNT3):​c.*281T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 437,994 control chromosomes in the GnomAD database, including 42,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12956 hom., cov: 32)
  • Exomes 𝑓: 0.44 (29378 hom.)
• Consequence: GALNT3 NM_004482.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.755
• Publications: 15 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• tumoral calcinosis, hyperphosphatemic, familial, 1

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

ENSG00000307262 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-165748500-A-T is Benign according to our data. Variant chr2-165748500-A-T is described in ClinVar as Benign. ClinVar VariationId is 331778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004482.4. 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
	GALNT3	NM_004482.4	MANE Select	c.*281T>A		3_prime_UTR	Exon 11 of 11	NP_004473.2	Q14435-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT3	ENST00000392701.8	TSL:1 MANE Select	c.*281T>A		3_prime_UTR	Exon 11 of 11	ENSP00000376465.3	Q14435-1
	GALNT3	ENST00000409882.5	TSL:1	c.*281T>A		3_prime_UTR	Exon 8 of 8	ENSP00000386955.1	E7EUL0
	GALNT3	ENST00000902717.1		c.*281T>A		3_prime_UTR	Exon 11 of 11	ENSP00000572776.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59431 AN: 151794 Hom.: 12948 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.393

GnomAD4 exome AF: 0.443 AC: 126810 AN: 286084 Hom.: 29378 Cov.: 2 AF XY: 0.439 AC XY: 65881 AN XY: 150144

African (AFR) AF: 0.196 AC: 1840 AN: 9390

American (AMR) AF: 0.316 AC: 3403 AN: 10784

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 4919 AN: 9736

East Asian (EAS) AF: 0.321 AC: 6385 AN: 19884

South Asian (SAS) AF: 0.370 AC: 13318 AN: 35974

European-Finnish (FIN) AF: 0.492 AC: 5495 AN: 11178

Middle Eastern (MID) AF: 0.319 AC: 399 AN: 1250

European-Non Finnish (NFE) AF: 0.489 AC: 83524 AN: 170940

Other (OTH) AF: 0.444 AC: 7527 AN: 16948

GnomAD4 genome AF: 0.391 AC: 59453 AN: 151910 Hom.: 12956 Cov.: 32 AF XY: 0.392 AC XY: 29126 AN XY: 74242

African (AFR) AF: 0.205 AC: 8500 AN: 41482

American (AMR) AF: 0.348 AC: 5306 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1742 AN: 3468

East Asian (EAS) AF: 0.355 AC: 1835 AN: 5176

South Asian (SAS) AF: 0.365 AC: 1758 AN: 4814

European-Finnish (FIN) AF: 0.485 AC: 5131 AN: 10578

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33699 AN: 67852

Other (OTH) AF: 0.396 AC: 835 AN: 2110

Alfa AF: 0.449 Hom.: 2152

Bravo AF: 0.369

Asia WGS AF: 0.342 AC: 1184 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Tumoral calcinosis, hyperphosphatemic, familial, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.3
DANN	Benign	0.67
PhyloP100		0.76
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: rs13429321; hg19: chr2-166605010;