22-32663679-G-C

Variant names:

• chr22-32663679-G-C
• rs5749482
• NM_003490.4:c.712-66943C>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.712-66943C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,038 control chromosomes in the GnomAD database, including 7,279 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 0.26 (7279 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 31 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]

LOC105373002 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 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.712-66943C>G		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.712-66943C>G		intron	N/A	NP_001356836.1
	SYN3	NM_001369908.1		c.712-66943C>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.712-66943C>G		intron	N/A	ENSP00000351614.2
	SYN3	ENST00000462268.1	TSL:3	n.226-33811C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39133 AN: 151918 Hom.: 7252 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.258 AC: 39214 AN: 152038 Hom.: 7279 Cov.: 32 AF XY: 0.260 AC XY: 19299 AN XY: 74320

African (AFR) AF: 0.455 AC: 18855 AN: 41424

American (AMR) AF: 0.336 AC: 5131 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3468

East Asian (EAS) AF: 0.701 AC: 3616 AN: 5162

South Asian (SAS) AF: 0.145 AC: 701 AN: 4820

European-Finnish (FIN) AF: 0.122 AC: 1286 AN: 10564

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8431 AN: 68008

Other (OTH) AF: 0.249 AC: 527 AN: 2114

Alfa AF: 0.0669 Hom.: 100

Bravo AF: 0.294

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.55
PhyloP100		-0.093
Mutation Taster		=100/0	polymorphism

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: rs5749482; hg19: chr22-33059665;