3-12161366-C-G

Variant names:

• chr3-12161366-C-G
• rs308950
• NM_133625.6:c.775-180C>G

Variant summary

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

The NM_133625.6(SYN2):​c.775-180C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,146 control chromosomes in the GnomAD database, including 51,775 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 0.82 (51775 hom., cov: 31)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 5 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN2	NM_133625.6	c.775-180C>G		intron_variant	Intron 5 of 12	ENST00000621198.5	NP_598328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.775-180C>G		intron_variant	Intron 5 of 12	1	NM_133625.6	ENSP00000480050.1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124627 AN: 152028 Hom.: 51725 Cov.: 31

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.820 AC: 124736 AN: 152146 Hom.: 51775 Cov.: 31 AF XY: 0.825 AC XY: 61376 AN XY: 74374

African (AFR) AF: 0.671 AC: 27822 AN: 41466

American (AMR) AF: 0.883 AC: 13512 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3172 AN: 3472

East Asian (EAS) AF: 0.811 AC: 4190 AN: 5168

South Asian (SAS) AF: 0.919 AC: 4437 AN: 4828

European-Finnish (FIN) AF: 0.912 AC: 9657 AN: 10594

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 59056 AN: 67998

Other (OTH) AF: 0.842 AC: 1778 AN: 2112

Alfa AF: 0.811 Hom.: 2604

Bravo AF: 0.810

Asia WGS AF: 0.888 AC: 3089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.32
DANN	Benign	0.67
PhyloP100		-1.1

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: rs308950; hg19: chr3-12202866; COSMIC: COSV55138785; COSMIC: COSV55138785;