3-12135583-C-T

Position:

• chr3-12135583-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

SYN2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN2	NM_133625.6	c.378-5068C>T		intron_variant		ENST00000621198.5	NP_598328.1
SYN2	NM_003178.6	c.378-5068C>T		intron_variant			NP_003169.2
SYN2	XM_006713311.4	c.378-5068C>T		intron_variant			XP_006713374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.378-5068C>T		intron_variant		1	NM_133625.6	ENSP00000480050.1
SYN2	ENST00000620175.4	c.378-5068C>T		intron_variant		1		ENSP00000484916.1
SYN2	ENST00000424884.1	n.127-5068C>T		intron_variant		4

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

Gnomad4 AFR AF: 0.975

Gnomad4 AMR AF: 0.943

Gnomad4 ASJ AF: 0.947

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.950

Gnomad4 FIN AF: 0.933

Gnomad4 NFE AF: 0.900

Gnomad4 OTH AF: 0.942

Alfa AF: 0.920 Hom.: 8000

Bravo AF: 0.938

Asia WGS AF: 0.976 AC: 3394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs308969; hg19: chr3-12177083;