3-12183853-C-G

Position:

• chr3-12183853-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000621198.5(SYN2):​c.1369+481C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 1,025,818 control chromosomes in the GnomAD database, including 1,908 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 0.085 (1005 hom., cov: 32)
  • Exomes 𝑓: 0.036 (903 hom.)
• Consequence: SYN2 ENST00000621198.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN2	NM_133625.6	c.1369+481C>G		intron_variant		ENST00000621198.5	NP_598328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.1369+481C>G		intron_variant		1	NM_133625.6	ENSP00000480050	P2
	ENST00000690965.1	n.528-4486G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12954 AN: 152002 Hom.: 1004 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0436

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.0368

Gnomad FIN AF: 0.0256

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.0757

GnomAD4 exome AF: 0.0356 AC: 31111 AN: 873698 Hom.: 903 Cov.: 30 AF XY: 0.0348 AC XY: 14134 AN XY: 405842

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.0246

Gnomad4 ASJ exome AF: 0.0381

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.0259

Gnomad4 FIN exome AF: 0.0272

Gnomad4 NFE exome AF: 0.0311

Gnomad4 OTH exome AF: 0.0471

GnomAD4 genome AF: 0.0852 AC: 12955 AN: 152120 Hom.: 1005 Cov.: 32 AF XY: 0.0830 AC XY: 6170 AN XY: 74348

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.0435

Gnomad4 ASJ AF: 0.0377

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.0362

Gnomad4 FIN AF: 0.0256

Gnomad4 NFE AF: 0.0349

Gnomad4 OTH AF: 0.0749

Alfa AF: 0.0176 Hom.: 11

Bravo AF: 0.0945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.58
DANN	Benign	0.55

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: rs2289708; hg19: chr3-12225353;