3-12141511-A-G

Variant names:

• chr3-12141511-A-G
• rs308964
• NM_133625.6:c.436-394A>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.436-394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 152,294 control chromosomes in the GnomAD database, including 66,521 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 0.93 (66521 hom., cov: 32)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133625.6. 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.436-394A>G		intron	N/A	NP_598328.1
	SYN2	NM_003178.6		c.436-394A>G		intron	N/A	NP_003169.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN2	ENST00000621198.5	TSL:1 MANE Select	c.436-394A>G		intron	N/A	ENSP00000480050.1
	SYN2	ENST00000620175.4	TSL:1	c.436-394A>G		intron	N/A	ENSP00000484916.1
	SYN2	ENST00000424884.1	TSL:4	n.185-394A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.934 AC: 142126 AN: 152176 Hom.: 66461 Cov.: 32

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.941

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

GnomAD4 genome AF: 0.934 AC: 142245 AN: 152294 Hom.: 66521 Cov.: 32 AF XY: 0.937 AC XY: 69764 AN XY: 74456

African (AFR) AF: 0.975 AC: 40508 AN: 41564

American (AMR) AF: 0.943 AC: 14435 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 3290 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5177 AN: 5178

South Asian (SAS) AF: 0.951 AC: 4584 AN: 4820

European-Finnish (FIN) AF: 0.933 AC: 9909 AN: 10618

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61222 AN: 68024

Other (OTH) AF: 0.942 AC: 1989 AN: 2112

Alfa AF: 0.910 Hom.: 3776

Bravo AF: 0.938

Asia WGS AF: 0.976 AC: 3395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.73
DANN	Benign	0.31
PhyloP100		-0.92

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: rs308964; hg19: chr3-12183011;