rs310763

Positions:

• chr3-12189204-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN2	NM_133625.6	c.1614-1286T>C		intron_variant		ENST00000621198.5	NP_598328.1
SYN2	XM_006713312.5	c.1131-1286T>C		intron_variant			XP_006713375.1
SYN2	XM_006713313.3	c.843-1286T>C		intron_variant			XP_006713376.1
SYN2	XM_017007087.2	c.942-1286T>C		intron_variant			XP_016862576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.1614-1286T>C		intron_variant		1	NM_133625.6	ENSP00000480050	P2
	ENST00000690965.1	n.527+3164A>G		intron_variant, non_coding_transcript_variant
SYN2	ENST00000439861.5	n.1233-1286T>C		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.854

Alfa AF: 0.802 Hom.: 47225

Bravo AF: 0.844

Asia WGS AF: 0.835 AC: 2904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs310763; hg19: chr3-12230704;