rs931676

Positions:

• chr3-12146943-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SYN2	NM_133625.6	c.684+1108T>C		intron_variant		ENST00000621198.5	NP_598328.1
SYN2	XM_006713312.5	c.177T>C	p.Tyr59=	synonymous_variant	1/10		XP_006713375.1
SYN2	NM_003178.6	c.684+1108T>C		intron_variant			NP_003169.2
SYN2	XM_006713311.4	c.684+1108T>C		intron_variant			XP_006713374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN2	ENST00000621198.5	c.684+1108T>C		intron_variant		1	NM_133625.6	ENSP00000480050	P2
SYN2	ENST00000620175.4	c.684+1108T>C		intron_variant		1		ENSP00000484916	A2
SYN2	ENST00000424884.1	n.433+1108T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.0815

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.0939

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.0394

Gnomad4 NFE AF: 0.0522

Gnomad4 OTH AF: 0.0803

Alfa AF: 0.0637 Hom.: 57

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs931676; hg19: chr3-12188443; COSMIC: COSV70285457; COSMIC: COSV70285457;