rs6721582

Variant names:

• chr2-165764726-G-A
• rs6721582
• NM_004482.4:c.688+158C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004482.4(GALNT3):​c.688+158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,000 control chromosomes in the GnomAD database, including 6,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (6251 hom., cov: 33)
• Consequence: GALNT3 NM_004482.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0370
• Publications: 6 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 2-165764726-G-A is Benign according to our data. Variant chr2-165764726-G-A is described in ClinVar as Benign. ClinVar VariationId is 1245536.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 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.688+158C>T		intron	N/A	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.688+158C>T		intron	N/A	ENSP00000376465.3	Q14435-1
	GALNT3	ENST00000902717.1		c.748+158C>T		intron	N/A	ENSP00000572776.1
	GALNT3	ENST00000715282.1		c.688+158C>T		intron	N/A	ENSP00000520447.1	Q14435-1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43094 AN: 151882 Hom.: 6249 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.284 AC: 43118 AN: 152000 Hom.: 6251 Cov.: 33 AF XY: 0.287 AC XY: 21324 AN XY: 74308

African (AFR) AF: 0.303 AC: 12537 AN: 41434

American (AMR) AF: 0.270 AC: 4129 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 924 AN: 3468

East Asian (EAS) AF: 0.387 AC: 1998 AN: 5164

South Asian (SAS) AF: 0.330 AC: 1591 AN: 4824

European-Finnish (FIN) AF: 0.307 AC: 3235 AN: 10554

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17768 AN: 67944

Other (OTH) AF: 0.289 AC: 611 AN: 2116

Alfa AF: 0.272 Hom.: 6979

Bravo AF: 0.285

Asia WGS AF: 0.339 AC: 1176 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.2
DANN	Benign	0.69
PhyloP100		0.037
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: rs6721582; hg19: chr2-166621236;