rs35419938

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_173593.4(B4GALNT3):c.1323G>C(p.Glu441Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00622 in 1,613,394 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 71 hom. )

Consequence

B4GALNT3
NM_173593.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00700

Publications

7 publications found

Variant links:

Genes affected

B4GALNT3 (HGNC:24137): (beta-1,4-N-acetyl-galactosaminyltransferase 3) B4GALNT3 transfers N-acetylgalactosamine (GalNAc) onto glucosyl residues to form N,N-prime-diacetyllactosediamine (LacdiNAc, or LDN), a unique terminal structure of cell surface N-glycans (Ikehara et al., 2006 [PubMed 16728562]).[supplied by OMIM, Aug 2008]

B4GALNT3 links:

ENSG00000304192 (HGNC:):

ENSG00000304192 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 (MetaRNN=0.003033489).

BP6

Variant 12-553246-G-C is Benign according to our data. Variant chr12-553246-G-C is described in ClinVar as Benign. ClinVar VariationId is 774703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00634 (9261/1461048) while in subpopulation MID AF = 0.0229 (132/5766). AF 95% confidence interval is 0.0197. There are 71 homozygotes in GnomAdExome4. There are 4952 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALNT3	NM_173593.4 link	c.1323G>C	p.Glu441Asp	missense_variant	Exon 14 of 20	ENST00000266383.10	NP_775864.3	Q6L9W6Q8N9V0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALNT3	ENST00000266383.10 link	c.1323G>C	p.Glu441Asp	missense_variant	Exon 14 of 20	1	NM_173593.4	ENSP00000266383.5		Q6L9W6

Frequencies

GnomAD3 genomes

AF:

0.00512

AC:

779

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00686

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00645

AC:

1618

AN:

250926

AF XY:

0.00740

show subpopulations

Gnomad AFR exome

AF:

0.00198

Gnomad AMR exome

AF:

0.00382

Gnomad ASJ exome

AF:

0.0165

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00626

Gnomad OTH exome

AF:

0.00490

GnomAD4 exome

AF:

0.00634

AC:

9261

AN:

1461048

Hom.:

Cov.:

AF XY:

0.00681

AC XY:

4952

AN XY:

726848

show subpopulations

African (AFR)

AF:

0.00245

AC:

AN:

33478

American (AMR)

AF:

0.00396

AC:

177

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0172

AC:

450

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0190

AC:

1643

AN:

86256

European-Finnish (FIN)

AF:

0.000493

AC:

AN:

52728

Middle Eastern (MID)

AF:

0.0229

AC:

132

AN:

5766

European-Non Finnish (NFE)

AF:

0.00566

AC:

6289

AN:

1111878

Other (OTH)

AF:

0.00763

AC:

461

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

571

1141

1712

2282

2853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

232

464

696

928

1160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00511

AC:

779

AN:

152346

Hom.:

Cov.:

AF XY:

0.00517

AC XY:

385

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

41572

American (AMR)

AF:

0.00398

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.0174

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00686

AC:

467

AN:

68030

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

106

141

176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00688

Hom.:

Bravo

AF:

0.00515

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00779

AC:

ExAC

AF:

0.00673

AC:

817

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00818

EpiControl

AF:

0.00794

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.8

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0080

T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.52

T;T

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;.

PhyloP100

0.0070

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.057

Sift

Benign

0.17

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.0010

B;B

Vest4

0.11

MutPred

0.061

Loss of glycosylation at P443 (P = 0.1716);.;

MVP

0.27

MPC

0.14

ClinPred

0.0042

GERP RS

1.8

Varity_R

0.070

gMVP

0.33

Mutation Taster

=98/2

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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