chr3-12146943-T-C

Variant names:

• chr3-12146943-T-C
• rs931676
• NM_133625.6:c.684+1108T>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.684+1108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 152,186 control chromosomes in the GnomAD database, including 588 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 0.079 (588 hom., cov: 32)
• Consequence: SYN2 NM_133625.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625
• 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN2	NM_133625.6	c.684+1108T>C		intron_variant	Intron 4 of 12	ENST00000621198.5	NP_598328.1
SYN2	XM_006713312.5	c.177T>C	p.Tyr59Tyr	synonymous_variant	Exon 1 of 10		XP_006713375.1
SYN2	NM_003178.6	c.684+1108T>C		intron_variant	Intron 4 of 10		NP_003169.2
SYN2	XM_006713311.4	c.684+1108T>C		intron_variant	Intron 4 of 10		XP_006713374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.684+1108T>C		intron_variant	Intron 4 of 12	1	NM_133625.6	ENSP00000480050.1
SYN2	ENST00000620175.4	c.684+1108T>C		intron_variant	Intron 4 of 10	1		ENSP00000484916.1
SYN2	ENST00000424884.1	n.433+1108T>C		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 12010 AN: 152068 Hom.: 585 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0816

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0937

Gnomad SAS AF: 0.0733

Gnomad FIN AF: 0.0394

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0521

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0790 AC: 12027 AN: 152186 Hom.: 588 Cov.: 32 AF XY: 0.0798 AC XY: 5939 AN XY: 74422

African (AFR) AF: 0.128 AC: 5300 AN: 41484

American (AMR) AF: 0.0815 AC: 1247 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 469 AN: 3470

East Asian (EAS) AF: 0.0939 AC: 486 AN: 5174

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4826

European-Finnish (FIN) AF: 0.0394 AC: 418 AN: 10612

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0522 AC: 3546 AN: 67996

Other (OTH) AF: 0.0803 AC: 170 AN: 2116

Alfa AF: 0.0658 Hom.: 61

Bravo AF: 0.0832

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.2
DANN	Benign	0.68
PhyloP100		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs931676; hg19: chr3-12188443; COSMIC: COSV70285457; COSMIC: COSV70285457;