rs4621175

Variant names:

• chr2-165792282-A-C
• rs4621175
• NM_004482.4:c.-109+1733T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-165792282-A-C
• chr2-165792282-A-G

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.-109+1733T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,120 control chromosomes in the GnomAD database, including 49,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.80 (49811 hom., cov: 33)
• Consequence: GALNT3 NM_004482.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.72
• Publications: 8 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=-0.83).
• BP6: Variant 2-165792282-A-C is Benign according to our data. Variant chr2-165792282-A-C is described in ClinVar as Benign. ClinVar VariationId is 1232432.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.885 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.-109+1733T>G		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.-109+1733T>G		intron	N/A	ENSP00000376465.3	Q14435-1
	GALNT3	ENST00000902717.1		c.-109+1733T>G		intron	N/A	ENSP00000572776.1
	GALNT3	ENST00000715282.1		c.-108-21474T>G		intron	N/A	ENSP00000520447.1	Q14435-1

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121939 AN: 152002 Hom.: 49790 Cov.: 33

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.958

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.802 AC: 122012 AN: 152120 Hom.: 49811 Cov.: 33 AF XY: 0.801 AC XY: 59540 AN XY: 74368

African (AFR) AF: 0.678 AC: 28124 AN: 41472

American (AMR) AF: 0.713 AC: 10887 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3118 AN: 3462

East Asian (EAS) AF: 0.643 AC: 3322 AN: 5170

South Asian (SAS) AF: 0.805 AC: 3886 AN: 4826

European-Finnish (FIN) AF: 0.872 AC: 9237 AN: 10590

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.891 AC: 60565 AN: 68006

Other (OTH) AF: 0.832 AC: 1757 AN: 2112

Alfa AF: 0.860 Hom.: 94832

Bravo AF: 0.779

Asia WGS AF: 0.728 AC: 2532 AN: 3478

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	-0.83
CADD	Benign	4.4
DANN	Benign	0.80
PhyloP100		-1.7
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: rs4621175; hg19: chr2-166648792;