2-165747911-T-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_004482.4(GALNT3):c.*870A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 174,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 0 hom. )

Consequence

GALNT3
NM_004482.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.78

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00169 (257/152192) while in subpopulation NFE AF = 0.00322 (219/67964). AF 95% confidence interval is 0.00287. There are 0 homozygotes in GnomAd4. There are 108 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GALNT3	NM_004482.4 link	c.*870A>T	3_prime_UTR_variant	Exon 11 of 11	ENST00000392701.8	NP_004473.2	Q14435-1
GALNT3	XM_005246449.2 link	c.*870A>T	3_prime_UTR_variant	Exon 11 of 11		XP_005246506.1	Q14435-1
GALNT3	XM_011510929.2 link	c.*870A>T	3_prime_UTR_variant	Exon 11 of 11		XP_011509231.1	Q14435-1
GALNT3	XM_017003770.2 link	c.*870A>T	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.*870A>T	3_prime_UTR_variant	Exon 11 of 11	1	NM_004482.4	ENSP00000376465.3	Q14435-1
GALNT3	ENST00000409882.5 link	c.*870A>T	3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000386955.1	E7EUL0
ENSG00000307262	ENST00000824811.1 link	n.130+988T>A	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00169

AC:

257

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00322

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.00225

AC:

AN:

22220

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

AN XY:

10022

show subpopulations

African (AFR)

AF:

0.00136

AC:

AN:

734

American (AMR)

AF:

0.00

AC:

AN:

500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1300

East Asian (EAS)

AF:

0.00

AC:

AN:

5090

South Asian (SAS)

AF:

0.00

AC:

AN:

184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.00370

AC:

AN:

12442

Other (OTH)

AF:

0.00163

AC:

AN:

1838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00169

AC:

257

AN:

152192

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

108

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

41570

American (AMR)

AF:

0.000196

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00322

AC:

219

AN:

67964

Other (OTH)

AF:

0.00143

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00249

Hom.:

Bravo

AF:

0.00152

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Tumoral calcinosis, hyperphosphatemic, familial, 1

Uncertain:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.27

(source)

DANN

Benign

0.66

PhyloP100

-1.8

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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2-165747911-T-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over