3-12142241-C-G

Variant names:

• chr3-12142241-C-G
• rs308965
• NM_133625.6:c.527+245C>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.527+245C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.931 in 152,312 control chromosomes in the GnomAD database, including 66,138 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 (66138 hom., cov: 32)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 4 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 (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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN2	NM_133625.6	MANE Select	c.527+245C>G		intron	N/A	NP_598328.1	Q92777-1
	SYN2	NM_003178.6		c.527+245C>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.527+245C>G		intron	N/A	ENSP00000480050.1	Q92777-1
	SYN2	ENST00000620175.4	TSL:1	c.527+245C>G		intron	N/A	ENSP00000484916.1	Q92777-2
	SYN2	ENST00000424884.1	TSL:4	n.276+245C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141741 AN: 152194 Hom.: 66080 Cov.: 32

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.942

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: 0.940

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

GnomAD4 genome AF: 0.931 AC: 141857 AN: 152312 Hom.: 66138 Cov.: 32 AF XY: 0.934 AC XY: 69603 AN XY: 74484

African (AFR) AF: 0.966 AC: 40133 AN: 41564

American (AMR) AF: 0.942 AC: 14423 AN: 15304

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

East Asian (EAS) AF: 1.00 AC: 5179 AN: 5180

South Asian (SAS) AF: 0.951 AC: 4584 AN: 4822

European-Finnish (FIN) AF: 0.933 AC: 9908 AN: 10616

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

European-Non Finnish (NFE) AF: 0.900 AC: 61221 AN: 68034

Other (OTH) AF: 0.940 AC: 1988 AN: 2114

Alfa AF: 0.917 Hom.: 7450

Bravo AF: 0.935

Asia WGS AF: 0.975 AC: 3390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.29
DANN	Benign	0.28
PhyloP100		-1.3

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: rs308965; hg19: chr3-12183741;