rs16851009

Variant names:

• chr2-165774197-C-T
• rs16851009
• NM_004482.4:c.-108-3389G>A

Variant summary

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

The NM_004482.4(GALNT3):​c.-108-3389G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,156 control chromosomes in the GnomAD database, including 1,666 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 0.13 (1666 hom., cov: 32)
• Consequence: GALNT3 NM_004482.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT3	NM_004482.4	c.-108-3389G>A		intron_variant	Intron 1 of 10	ENST00000392701.8	NP_004473.2
GALNT3	XM_011510929.2	c.-108-3389G>A		intron_variant	Intron 1 of 10		XP_011509231.1
GALNT3	XM_017003770.2	c.-108-3389G>A		intron_variant	Intron 1 of 10		XP_016859259.1
GALNT3	XM_047443883.1	c.-108-3389G>A		intron_variant	Intron 1 of 6		XP_047299839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT3	ENST00000392701.8	c.-108-3389G>A		intron_variant	Intron 1 of 10	1	NM_004482.4	ENSP00000376465.3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20378 AN: 152036 Hom.: 1668 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0734

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.134 AC: 20396 AN: 152156 Hom.: 1666 Cov.: 32 AF XY: 0.137 AC XY: 10223 AN XY: 74404

African (AFR) AF: 0.144 AC: 5962 AN: 41514

American (AMR) AF: 0.201 AC: 3074 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0734 AC: 255 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1712 AN: 5158

South Asian (SAS) AF: 0.182 AC: 874 AN: 4808

European-Finnish (FIN) AF: 0.124 AC: 1317 AN: 10588

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6884 AN: 68006

Other (OTH) AF: 0.116 AC: 246 AN: 2112

Alfa AF: 0.114 Hom.: 3075

Bravo AF: 0.145

Asia WGS AF: 0.243 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.60
PhyloP100		0.033
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: rs16851009; hg19: chr2-166630707;