3-12140098-A-G

Variant names:

• chr3-12140098-A-G
• rs1021679
• NM_133625.6:c.378-553A>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.378-553A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 152,152 control chromosomes in the GnomAD database, including 586 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 0.079 (586 hom., cov: 32)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN2	NM_133625.6	MANE Select	c.378-553A>G		intron	N/A	NP_598328.1
	SYN2	NM_003178.6		c.378-553A>G		intron	N/A	NP_003169.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN2	ENST00000621198.5	TSL:1 MANE Select	c.378-553A>G		intron	N/A	ENSP00000480050.1
	SYN2	ENST00000620175.4	TSL:1	c.378-553A>G		intron	N/A	ENSP00000484916.1
	SYN2	ENST00000424884.1	TSL:4	n.127-553A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12043 AN: 152032 Hom.: 583 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0953

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0525

Gnomad OTH AF: 0.0770

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

GnomAD4 genome AF: 0.0793 AC: 12059 AN: 152152 Hom.: 586 Cov.: 32 AF XY: 0.0803 AC XY: 5969 AN XY: 74374

African (AFR) AF: 0.127 AC: 5289 AN: 41488

American (AMR) AF: 0.0810 AC: 1237 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 470 AN: 3470

East Asian (EAS) AF: 0.0955 AC: 495 AN: 5184

South Asian (SAS) AF: 0.0744 AC: 359 AN: 4826

European-Finnish (FIN) AF: 0.0419 AC: 443 AN: 10578

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0525 AC: 3569 AN: 68008

Other (OTH) AF: 0.0777 AC: 164 AN: 2112

Alfa AF: 0.0304 Hom.: 27

Bravo AF: 0.0830

Asia WGS AF: 0.114 AC: 397 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
DANN	Benign	0.52
PhyloP100		-0.72

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: rs1021679; hg19: chr3-12181598;