NM_003458.4:c.11587G>C

Variant names:

• chr3-49663865-G-C
• rs2005557
• NM_003458.4:c.11587G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003458.4(BSN):​c.11587G>C​(p.Ala3863Pro) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BSN NM_003458.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403
• Publications: 42 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029015273).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSN	NM_003458.4	MANE Select	c.11587G>C	p.Ala3863Pro	missense	Exon 8 of 12	NP_003449.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSN	ENST00000296452.5	TSL:1 MANE Select	c.11587G>C	p.Ala3863Pro	missense	Exon 8 of 12	ENSP00000296452.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.73
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.92	N
PhyloP100		0.40
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.026
Sift	Benign	0.82	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.25		Gain of glycosylation at A3863 (P = 0.0021)
MVP		0.16
MPC		0.36
ClinPred		0.046	T
GERP RS		1.3
Varity_R		0.053
gMVP		0.10
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs2005557; hg19: chr3-49701298;