chr2-165748500-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.755

Publications

15 publications found

Variant links:

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

GALNT3 links:

ENSG00000307262 (HGNC:):

ENSG00000307262 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
GALNT3	NM_004482.4 link	c.*281T>A	3_prime_UTR_variant	Exon 11 of 11	ENST00000392701.8	NP_004473.2	Q14435-1
GALNT3	XM_005246449.2 link	c.*281T>A	3_prime_UTR_variant	Exon 11 of 11		XP_005246506.1	Q14435-1
GALNT3	XM_011510929.2 link	c.*281T>A	3_prime_UTR_variant	Exon 11 of 11		XP_011509231.1	Q14435-1
GALNT3	XM_017003770.2 link	c.*281T>A	3_prime_UTR_variant	Exon 11 of 11		XP_016859259.1	Q14435-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GALNT3	ENST00000392701.8 link	c.*281T>A	3_prime_UTR_variant	Exon 11 of 11	1	NM_004482.4	ENSP00000376465.3	Q14435-1
GALNT3	ENST00000409882.5 link	c.*281T>A	3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000386955.1	E7EUL0
GALNT3	ENST00000715282.1 link	c.*281T>A	3_prime_UTR_variant	Exon 11 of 11			ENSP00000520447.1
ENSG00000307262	ENST00000824811.1 link	n.131-1297A>T	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

59431

AN:

151794

Hom.:

12948

Cov.:

show subpopulations

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.:

AF XY:

0.439

AC XY:

65881

AN XY:

150144

show subpopulations

African (AFR)

AF:

0.196

AC:

1840

AN:

9390

American (AMR)

AF:

0.316

AC:

3403

AN:

10784

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

4919

AN:

9736

East Asian (EAS)

AF:

0.321

AC:

6385

AN:

19884

South Asian (SAS)

AF:

0.370

AC:

13318

AN:

35974

European-Finnish (FIN)

AF:

0.492

AC:

5495

AN:

11178

Middle Eastern (MID)

AF:

0.319

AC:

399

AN:

1250

European-Non Finnish (NFE)

AF:

0.489

AC:

83524

AN:

170940

Other (OTH)

AF:

0.444

AC:

7527

AN:

16948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

3206

6413

9619

12826

16032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.391

AC:

59453

AN:

151910

Hom.:

12956

Cov.:

AF XY:

0.392

AC XY:

29126

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.205

AC:

8500

AN:

41482

American (AMR)

AF:

0.348

AC:

5306

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.502

AC:

1742

AN:

3468

East Asian (EAS)

AF:

0.355

AC:

1835

AN:

5176

South Asian (SAS)

AF:

0.365

AC:

1758

AN:

4814

European-Finnish (FIN)

AF:

0.485

AC:

5131

AN:

10578

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.497

AC:

33699

AN:

67852

Other (OTH)

AF:

0.396

AC:

835

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1709

3418

5127

6836

8545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Tumoral calcinosis, hyperphosphatemic, familial, 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.67

PhyloP100

0.76

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr2-165748500-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over