chr3-12140251-C-G

Variant names:

• chr3-12140251-C-G
• rs308963
• NM_133625.6:c.378-400C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133625.6(SYN2):​c.378-400C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,024 control chromosomes in the GnomAD database, including 33,542 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (33542 hom., cov: 33)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.939
• Publications: 5 publications found

Genes affected

SYN2 (HGNC:11495): (synapsin II) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. This member of the synapsin family encodes a neuron-specific phosphoprotein that selectively binds to small synaptic vesicles in the presynaptic nerve terminal. Polymorphisms in this gene are associated with abnormal presynaptic function and related neuronal disorders, including autism, epilepsy, bipolar disorder and schizophrenia. Alternative splicing of this gene results in multiple transcript variants. The tissue inhibitor of metalloproteinase 4 gene is located within an intron of this gene and is transcribed in the opposite direction. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN2	NM_133625.6	c.378-400C>G		intron_variant	Intron 1 of 12	ENST00000621198.5	NP_598328.1
SYN2	NM_003178.6	c.378-400C>G		intron_variant	Intron 1 of 10		NP_003169.2
SYN2	XM_006713311.4	c.378-400C>G		intron_variant	Intron 1 of 10		XP_006713374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.378-400C>G		intron_variant	Intron 1 of 12	1	NM_133625.6	ENSP00000480050.1
SYN2	ENST00000620175.4	c.378-400C>G		intron_variant	Intron 1 of 10	1		ENSP00000484916.1
SYN2	ENST00000424884.1	n.127-400C>G		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96860 AN: 151904 Hom.: 33526 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.698

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.637 AC: 96894 AN: 152024 Hom.: 33542 Cov.: 33 AF XY: 0.643 AC XY: 47809 AN XY: 74334

African (AFR) AF: 0.339 AC: 14028 AN: 41388

American (AMR) AF: 0.755 AC: 11542 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2534 AN: 3470

East Asian (EAS) AF: 0.677 AC: 3502 AN: 5172

South Asian (SAS) AF: 0.777 AC: 3746 AN: 4824

European-Finnish (FIN) AF: 0.788 AC: 8338 AN: 10576

Middle Eastern (MID) AF: 0.772 AC: 224 AN: 290

European-Non Finnish (NFE) AF: 0.745 AC: 50673 AN: 67994

Other (OTH) AF: 0.700 AC: 1476 AN: 2110

Alfa AF: 0.583 Hom.: 1926

Bravo AF: 0.622

Asia WGS AF: 0.704 AC: 2449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.66
PhyloP100		0.94

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: rs308963; hg19: chr3-12181751;