rs80689

Variant names:

• chr22-32884110-T-C
• rs80689
• NM_003490.4:c.462-14985A>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.462-14985A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,162 control chromosomes in the GnomAD database, including 4,410 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 0.23 (4410 hom., cov: 33)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	NM_003490.4	MANE Select	c.462-14985A>G		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.462-14985A>G		intron	N/A	NP_001356836.1	O14994
	SYN3	NM_001369908.1		c.462-14985A>G		intron	N/A	NP_001356837.1	O14994

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	ENST00000358763.7	TSL:5 MANE Select	c.462-14985A>G		intron	N/A	ENSP00000351614.2	O14994

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35070 AN: 152044 Hom.: 4403 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0429

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.231 AC: 35093 AN: 152162 Hom.: 4410 Cov.: 33 AF XY: 0.226 AC XY: 16804 AN XY: 74380

African (AFR) AF: 0.145 AC: 6032 AN: 41510

American (AMR) AF: 0.241 AC: 3676 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3468

East Asian (EAS) AF: 0.0432 AC: 224 AN: 5188

South Asian (SAS) AF: 0.184 AC: 888 AN: 4826

European-Finnish (FIN) AF: 0.288 AC: 3047 AN: 10584

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19403 AN: 67990

Other (OTH) AF: 0.236 AC: 498 AN: 2112

Alfa AF: 0.267 Hom.: 10455

Bravo AF: 0.224

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.053
DANN	Benign	0.18
PhyloP100		-3.4
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: rs80689; hg19: chr22-33280097;