NM_003458.4:c.23A>G

Variant names:

• chr3-49554625-A-G
• rs922281244
• NM_003458.4:c.23A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_003458.4(BSN):​c.23A>G​(p.Glu8Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 980,498 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: 𝑓 0.0000069 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: BSN NM_003458.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42
• Publications: 0 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3133909).

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.23A>G	p.Glu8Gly	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.23A>G	p.Glu8Gly	missense	Exon 1 of 12	ENSP00000296452.4	Q9UPA5

Frequencies

GnomAD3 genomes AF: 0.00000686 AC: 1 AN: 145750 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000120 AC: 10 AN: 834748 Hom.: 0 Cov.: 30 AF XY: 0.0000155 AC XY: 6 AN XY: 385924

African (AFR) AF: 0.00 AC: 0 AN: 15778

American (AMR) AF: 0.00 AC: 0 AN: 1076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5208

East Asian (EAS) AF: 0.00 AC: 0 AN: 3670

South Asian (SAS) AF: 0.00 AC: 0 AN: 17226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1630

European-Non Finnish (NFE) AF: 0.0000131 AC: 10 AN: 762318

Other (OTH) AF: 0.00 AC: 0 AN: 27394

GnomAD4 genome AF: 0.00000686 AC: 1 AN: 145750 Hom.: 0 Cov.: 32 AF XY: 0.0000141 AC XY: 1 AN XY: 70886

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40550

American (AMR) AF: 0.00 AC: 0 AN: 14738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3388

East Asian (EAS) AF: 0.00 AC: 0 AN: 5074

South Asian (SAS) AF: 0.00 AC: 0 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65632

Other (OTH) AF: 0.00 AC: 0 AN: 2024

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.31	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.4
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.085
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.034	D
Polyphen		0.99	D
Vest4		0.38
MutPred		0.20		Loss of sheet (P = 0.0126)
MVP		0.25
MPC		0.32
ClinPred		0.73	D
GERP RS		3.2
PromoterAI		-0.047	Neutral
Varity_R		0.27
gMVP		0.21
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs922281244; hg19: chr3-49592058;