chr3-12152585-T-C

Variant names:

• chr3-12152585-T-C
• rs99365
• NM_133625.6:c.774+1259T>C

Variant summary

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

The NM_133625.6(SYN2):​c.774+1259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,168 control chromosomes in the GnomAD database, including 53,596 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 (53596 hom., cov: 31)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.884 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.774+1259T>C		intron	N/A	NP_598328.1
	SYN2	NM_003178.6		c.774+1259T>C		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.774+1259T>C		intron	N/A	ENSP00000480050.1
	SYN2	ENST00000620175.4	TSL:1	c.774+1259T>C		intron	N/A	ENSP00000484916.1
	SYN2	ENST00000439861.5	TSL:2	n.225+1259T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127136 AN: 152050 Hom.: 53556 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.895

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.836 AC: 127226 AN: 152168 Hom.: 53596 Cov.: 31 AF XY: 0.841 AC XY: 62570 AN XY: 74404

African (AFR) AF: 0.728 AC: 30204 AN: 41476

American (AMR) AF: 0.895 AC: 13692 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3154 AN: 3472

East Asian (EAS) AF: 0.808 AC: 4171 AN: 5160

South Asian (SAS) AF: 0.907 AC: 4373 AN: 4822

European-Finnish (FIN) AF: 0.910 AC: 9660 AN: 10610

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 59059 AN: 68018

Other (OTH) AF: 0.853 AC: 1802 AN: 2112

Alfa AF: 0.861 Hom.: 68166

Bravo AF: 0.829

Asia WGS AF: 0.880 AC: 3060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.025
DANN	Benign	0.52
PhyloP100		-2.4

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: rs99365; hg19: chr3-12194085;