rs310763

Variant names:

• chr3-12189204-T-C
• rs310763
• NM_133625.6:c.1614-1286T>C

Variant summary

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

The ENST00000621198.5(SYN2):​c.1614-1286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,156 control chromosomes in the GnomAD database, including 53,408 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 0.84 (53408 hom., cov: 32)
• Consequence: SYN2 ENST00000621198.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753
• Publications: 10 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]

ENSG00000288952 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000621198.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN2	NM_133625.6	MANE Select	c.1614-1286T>C		intron	N/A	NP_598328.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN2	ENST00000621198.5	TSL:1 MANE Select	c.1614-1286T>C		intron	N/A	ENSP00000480050.1
	SYN2	ENST00000439861.5	TSL:2	n.1233-1286T>C		intron	N/A
	ENSG00000288952	ENST00000690965.2		n.527+3164A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126949 AN: 152038 Hom.: 53349 Cov.: 32

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.835 AC: 127065 AN: 152156 Hom.: 53408 Cov.: 32 AF XY: 0.836 AC XY: 62155 AN XY: 74366

African (AFR) AF: 0.922 AC: 38326 AN: 41550

American (AMR) AF: 0.838 AC: 12792 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2662 AN: 3470

East Asian (EAS) AF: 0.872 AC: 4488 AN: 5146

South Asian (SAS) AF: 0.820 AC: 3953 AN: 4820

European-Finnish (FIN) AF: 0.813 AC: 8612 AN: 10590

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53343 AN: 67984

Other (OTH) AF: 0.854 AC: 1808 AN: 2116

Alfa AF: 0.804 Hom.: 56510

Bravo AF: 0.844

Asia WGS AF: 0.835 AC: 2904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.31
PhyloP100		-0.75

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: rs310763; hg19: chr3-12230704;