3-12182651-T-C

Position:

• chr3-12182651-T-C

Variant summary

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

The NM_133625.6(SYN2):​c.1309-661T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,132 control chromosomes in the GnomAD database, including 11,715 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 0.37 (11715 hom., cov: 33)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN2	NM_133625.6	c.1309-661T>C		intron_variant		ENST00000621198.5	NP_598328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.1309-661T>C		intron_variant		1	NM_133625.6	ENSP00000480050	P2
	ENST00000690965.1	n.528-3284A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56688 AN: 152014 Hom.: 11703 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.373 AC: 56722 AN: 152132 Hom.: 11715 Cov.: 33 AF XY: 0.381 AC XY: 28366 AN XY: 74362

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.395

Alfa AF: 0.394 Hom.: 12079

Bravo AF: 0.364

Asia WGS AF: 0.592 AC: 2058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.076
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs310762; hg19: chr3-12224151;