chr3-12135583-C-T

Variant names:

• chr3-12135583-C-T
• rs308969
• NM_133625.6:c.378-5068C>T

Variant summary

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

The NM_133625.6(SYN2):​c.378-5068C>T 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 152,284 control chromosomes in the GnomAD database, including 66,508 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 (66508 hom., cov: 32)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• 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=-0.86).
• 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.378-5068C>T		intron	N/A	NP_598328.1
	SYN2	NM_003178.6		c.378-5068C>T		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.378-5068C>T		intron	N/A	ENSP00000480050.1
	SYN2	ENST00000620175.4	TSL:1	c.378-5068C>T		intron	N/A	ENSP00000484916.1
	SYN2	ENST00000424884.1	TSL:4	n.127-5068C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.934 AC: 142108 AN: 152166 Hom.: 66448 Cov.: 32

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.965

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: 142227 AN: 152284 Hom.: 66508 Cov.: 32 AF XY: 0.937 AC XY: 69746 AN XY: 74446

African (AFR) AF: 0.975 AC: 40488 AN: 41542

American (AMR) AF: 0.943 AC: 14433 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 3289 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5187 AN: 5188

South Asian (SAS) AF: 0.950 AC: 4585 AN: 4824

European-Finnish (FIN) AF: 0.933 AC: 9903 AN: 10614

Middle Eastern (MID) AF: 0.969 AC: 283 AN: 292

European-Non Finnish (NFE) AF: 0.900 AC: 61218 AN: 68026

Other (OTH) AF: 0.942 AC: 1993 AN: 2116

Alfa AF: 0.922 Hom.: 8360

Bravo AF: 0.938

Asia WGS AF: 0.976 AC: 3394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.57
PhyloP100		0.42

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: rs308969; hg19: chr3-12177083;