rs80689

Positions:

• chr22-32884110-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN3	NM_003490.4	c.462-14985A>G		intron_variant		ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.462-14985A>G		intron_variant		5	NM_003490.4	ENSP00000351614	P1

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

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.0432

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.236

Alfa AF: 0.273 Hom.: 8219

Bravo AF: 0.224

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.053
DANN	Benign	0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs80689; hg19: chr22-33280097;