chr3-12188015-TTC-T

Position:

• chr3-12188015-TTC-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_133625.6(SYN2):​c.1613+405_1613+406del variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (36795 hom., cov: 0)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.614

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN2	NM_133625.6	c.1613+405_1613+406del		intron_variant		ENST00000621198.5	NP_598328.1
SYN2	XM_006713312.5	c.1130+405_1130+406del		intron_variant			XP_006713375.1
SYN2	XM_006713313.3	c.842+405_842+406del		intron_variant			XP_006713376.1
SYN2	XM_017007087.2	c.941+405_941+406del		intron_variant			XP_016862576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.1613+405_1613+406del		intron_variant		1	NM_133625.6	ENSP00000480050	P2
	ENST00000690965.1	n.527+4351_527+4352del		intron_variant, non_coding_transcript_variant
SYN2	ENST00000439861.5	n.1232+405_1232+406del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.726 AC: 104166 AN: 143558 Hom.: 36762 Cov.: 0

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.915

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.726 AC: 104248 AN: 143676 Hom.: 36795 Cov.: 0 AF XY: 0.729 AC XY: 51229 AN XY: 70282

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.809

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.759

Alfa AF: 0.709 Hom.: 4198

Bravo AF: 0.678

Asia WGS AF: 0.735 AC: 2557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs2307973; hg19: chr3-12229515;