22-33007293-G-C

Variant names:

• chr22-33007293-G-C
• rs133946
• NM_003490.4:c.-162-469C>G

Variant summary

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

The NM_003490.4(SYN3):​c.-162-469C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,038 control chromosomes in the GnomAD database, including 15,422 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 0.45 (15422 hom., cov: 33)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323
• Publications: 14 publications found

Genes affected

SYN3 (HGNC:11496): (synapsin III) 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. The protein encoded by this gene shares the synapsin family domain model, with domains A, C, and E exhibiting the highest degree of conservation. The protein contains a unique domain J, located between domains C and E. Based on this gene's localization to 22q12.3, a possible schizophrenia susceptibility locus, and the established neurobiological roles of the synapsins, this family member may represent a candidate gene for schizophrenia. The TIMP3 gene is located within an intron of this gene and is transcribed in the opposite direction. Alternative splicing of this gene results in multiple splice variants that encode different isoforms. [provided by RefSeq, Oct 2008]

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 (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003490.4. 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
	SYN3	NM_003490.4	MANE Select	c.-162-469C>G		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.-159-472C>G		intron	N/A	NP_001356836.1
	SYN3	NM_001369908.1		c.-162-469C>G		intron	N/A	NP_001356837.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	ENST00000358763.7	TSL:5 MANE Select	c.-162-469C>G		intron	N/A	ENSP00000351614.2
	SYN3	ENST00000441821.5	TSL:1	c.-162-469C>G		intron	N/A	ENSP00000395794.1
	SYN3	ENST00000412575.1	TSL:5	c.-162-469C>G		intron	N/A	ENSP00000388582.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67799 AN: 151918 Hom.: 15420 Cov.: 33

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.446 AC: 67817 AN: 152038 Hom.: 15422 Cov.: 33 AF XY: 0.446 AC XY: 33168 AN XY: 74318

African (AFR) AF: 0.386 AC: 16010 AN: 41470

American (AMR) AF: 0.417 AC: 6369 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1803 AN: 3472

East Asian (EAS) AF: 0.327 AC: 1692 AN: 5180

South Asian (SAS) AF: 0.433 AC: 2084 AN: 4812

European-Finnish (FIN) AF: 0.480 AC: 5063 AN: 10540

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33121 AN: 67964

Other (OTH) AF: 0.482 AC: 1019 AN: 2116

Alfa AF: 0.449 Hom.: 1925

Bravo AF: 0.438

Asia WGS AF: 0.358 AC: 1247 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	1.2
DANN	Benign	0.67
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs133946; hg19: chr22-33403278;