3-12148468-A-G

Position:

• chr3-12148468-A-G

Variant summary

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

The NM_133625.6(SYN2):​c.684+2633A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,338 control chromosomes in the GnomAD database, including 2,906 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 0.16 (2899 hom., cov: 32)
  • Exomes 𝑓: 0.27 (7 hom.)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYN2	NM_133625.6	c.684+2633A>G		intron_variant		ENST00000621198.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYN2	ENST00000621198.5	c.684+2633A>G		intron_variant		1	NM_133625.6	P2
SYN2	ENST00000620175.4	c.684+2633A>G		intron_variant		1		A2
SYN2	ENST00000424884.1	n.433+2633A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23862 AN: 152096 Hom.: 2897 Cov.: 32

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.274 AC: 34 AN: 124 Hom.: 7 AF XY: 0.255 AC XY: 24 AN XY: 94

Gnomad4 AFR exome AF: 0.100

Gnomad4 EAS exome AF: 0.600

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.157 AC: 23860 AN: 152214 Hom.: 2899 Cov.: 32 AF XY: 0.168 AC XY: 12478 AN XY: 74408

Gnomad4 AFR AF: 0.0441

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.0998

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.146

Alfa AF: 0.166 Hom.: 1355

Bravo AF: 0.144

Asia WGS AF: 0.436 AC: 1515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3773364; hg19: chr3-12189968;