dbSNP rs763929574: B3GNT9:p.Ala346Val (chr16-67149449-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033309.3(B3GNT9):c.1037C>T(p.Ala346Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000809 in 1,606,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

B3GNT9
NM_033309.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

Publications

0 publications found

Variant links:

Genes affected

B3GNT9 (HGNC:28714): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 9) Predicted to enable UDP-glycosyltransferase activity. Predicted to be involved in poly-N-acetyllactosamine biosynthetic process. Predicted to be integral component of membrane. Predicted to be active in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

B3GNT9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14441139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GNT9	NM_033309.3 link	c.1037C>T	p.Ala346Val	missense_variant	Exon 2 of 2	ENST00000449549.4	NP_171608.2	Q6UX72

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GNT9	ENST00000449549.4 link	c.1037C>T	p.Ala346Val	missense_variant	Exon 2 of 2	1	NM_033309.3	ENSP00000400157.3		Q6UX72

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000854

AC:

AN:

234314

AF XY:

0.0000157

show subpopulations

Gnomad AFR exome

AF:

0.0000714

Gnomad AMR exome

AF:

0.0000303

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1454550

Hom.:

Cov.:

AF XY:

0.00000692

AC XY:

AN XY:

722886

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33354

American (AMR)

AF:

0.0000458

AC:

AN:

43676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25910

East Asian (EAS)

AF:

0.00

AC:

AN:

39320

South Asian (SAS)

AF:

0.00

AC:

AN:

84988

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52796

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108676

Other (OTH)

AF:

0.00

AC:

AN:

60080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.554

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41468

American (AMR)

AF:

0.0000654

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000877

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 17, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1037C>T (p.A346V) alteration is located in exon 2 (coding exon 1) of the B3GNT9 gene. This alteration results from a C to T substitution at nucleotide position 1037, causing the alanine (A) at amino acid position 346 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Benign

0.044

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.030

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

4.8

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.5

REVEL

Benign

0.050

Sift

Benign

0.13

Sift4G

Benign

0.22

Polyphen

0.40

Vest4

0.38

MVP

0.26

MPC

1.8

ClinPred

0.29

GERP RS

5.0

Varity_R

0.14

gMVP

0.59

Mutation Taster

=80/20

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