Genetic Variant BSN:p.Gly42Cys (chr3-49554726-G-T) – 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_003458.4(BSN):c.124G>T(p.Gly42Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G42D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BSN
NM_003458.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

Publications

0 publications found

Variant links:

Genes affected

BSN (HGNC:1117): (bassoon presynaptic cytomatrix protein) Neurotransmitters are released from a specific site in the axon terminal called the active zone, which is composed of synaptic vesicles and a meshwork of cytoskeleton underlying the plasma membrane. The protein encoded by this gene is thought to be a scaffolding protein involved in organizing the presynaptic cytoskeleton. The gene is expressed primarily in neurons in the brain. A similar gene product in rodents is concentrated in the active zone of axon terminals and tightly associated with cytoskeletal structures, and is essential for regulating neurotransmitter release from a subset of synapses. [provided by RefSeq, Jul 2008]

BSN Gene-Disease associations (from GenCC):

epilepsy
Inheritance: AR, AD Classification: LIMITED Submitted by: G2P

BSN 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=0.24310395).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003458.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSN	NM_003458.4	MANE Select	c.124G>T	p.Gly42Cys	missense	Exon 1 of 12	NP_003449.2	Q9UPA5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSN	ENST00000296452.5	TSL:1 MANE Select	c.124G>T	p.Gly42Cys	missense	Exon 1 of 12	ENSP00000296452.4	Q9UPA5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1069826

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

509010

African (AFR)

AF:

0.00

AC:

AN:

22082

American (AMR)

AF:

0.00

AC:

AN:

9942

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14090

East Asian (EAS)

AF:

0.00

AC:

AN:

24096

South Asian (SAS)

AF:

0.00

AC:

AN:

24292

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2832

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

909732

Other (OTH)

AF:

0.00

AC:

AN:

41932

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.28

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.43

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

1.5

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-2.3

REVEL

Benign

0.067

Sift

Uncertain

0.0050

Sift4G

Benign

0.092

Polyphen

0.93

Vest4

0.23

MutPred

0.29

Loss of relative solvent accessibility (P = 0.0071)

MVP

0.23

MPC

0.29

ClinPred

0.33

GERP RS

2.6

PromoterAI

0.23

Neutral

(source)

Varity_R

0.21

gMVP

0.27

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over