rs4621175

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT3	NM_004482.4	c.-109+1733T>G		intron_variant		ENST00000392701.8	NP_004473.2
GALNT3	XM_011510929.2	c.-109+2207T>G		intron_variant			XP_011509231.1
GALNT3	XM_017003770.2	c.-109+2043T>G		intron_variant			XP_016859259.1
GALNT3	XM_047443883.1	c.-109+1733T>G		intron_variant			XP_047299839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT3	ENST00000392701.8	c.-109+1733T>G		intron_variant		1	NM_004482.4	ENSP00000376465	P1

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

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.901

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.872

Gnomad4 NFE AF: 0.891

Gnomad4 OTH AF: 0.832

Alfa AF: 0.871 Hom.: 76254

Bravo AF: 0.779

Asia WGS AF: 0.728 AC: 2532 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2020

This variant is associated with the following publications: (PMID: 28453302) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs4621175; hg19: chr2-166648792;