3-49642334-C-A

Position:

• chr3-49642334-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_003458.4(BSN):​c.700C>A​(p.Pro234Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,447,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BSN NM_003458.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, BSN
• BP4: Computational evidence support a benign effect (MetaRNN=0.27687353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BSN	NM_003458.4	c.700C>A	p.Pro234Thr	missense_variant	3/12	ENST00000296452.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSN	ENST00000296452.5	c.700C>A	p.Pro234Thr	missense_variant	3/12	1	NM_003458.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1447226 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 719062

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Mar 07, 2024

PM2, BP4, PP2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	0.99	D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.11
Sift	Benign	0.065	T
Sift4G	Benign	0.062	T
Polyphen		0.78	P
Vest4		0.42
MutPred		0.25		Gain of MoRF binding (P = 0.0538);
MVP		0.28
MPC		0.31
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.42
gMVP		0.52

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: rs775327878; hg19: chr3-49679767;