2-165748500-A-T

Position:

• chr2-165748500-A-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT3	NM_004482.4	c.*281T>A		3_prime_UTR_variant	11/11	ENST00000392701.8
GALNT3	XM_005246449.2	c.*281T>A		3_prime_UTR_variant	11/11
GALNT3	XM_011510929.2	c.*281T>A		3_prime_UTR_variant	11/11
GALNT3	XM_017003770.2	c.*281T>A		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT3	ENST00000392701.8	c.*281T>A		3_prime_UTR_variant	11/11	1	NM_004482.4	P1
GALNT3	ENST00000409882.5	c.*281T>A		3_prime_UTR_variant	8/8	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

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.316

Gnomad4 ASJ exome AF: 0.505

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.492

Gnomad4 NFE exome AF: 0.489

Gnomad4 OTH exome AF: 0.444

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

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.396

Alfa AF: 0.449 Hom.: 2152

Bravo AF: 0.369

Asia WGS AF: 0.342 AC: 1184 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Tumoral calcinosis, hyperphosphatemic, familial, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.3
DANN	Benign	0.67

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: rs13429321; hg19: chr2-166605010;