chr3-49625078-C-T

Variant names:

• chr3-49625078-C-T
• rs757868271
• NM_003458.4:c.328C>T

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_003458.4(BSN):​c.328C>T​(p.Arg110*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BSN NM_003458.4 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.408

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]

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BSN	NM_003458.4	c.328C>T	p.Arg110*	stop_gained	Exon 2 of 12	ENST00000296452.5	NP_003449.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BSN	ENST00000296452.5	c.328C>T	p.Arg110*	stop_gained	Exon 2 of 12	1	NM_003458.4	ENSP00000296452.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1455526 Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3 AN XY: 724010

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33206

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 43234

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25954

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39432

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 85160

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53372

Gnomad4 NFE exome AF: 0.00000270 AC: 3 AN: 1109330

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60116

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

BSN related epilepsy Uncertain:1

Aug 16, 2023

Baylor Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	31
DANN	Uncertain	0.99
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.094
FATHMM_MKL	Benign	0.26	N
Vest4		0.70
GERP RS		3.6
Mutation Taster		=28/172	disease causing (fs/PTC)

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

LitVar

Other links and lift over

dbSNP: rs757868271; hg19: chr3-49662511;