22-32709831-T-C

Position:

• chr22-32709831-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.712-113095A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,824 control chromosomes in the GnomAD database, including 7,643 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 0.27 (7643 hom., cov: 31)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN3	NM_003490.4	c.712-113095A>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.712-113095A>G		intron_variant		5	NM_003490.4	ENSP00000351614.2
SYN3	ENST00000462268.1	n.226-79963A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40259 AN: 151704 Hom.: 7624 Cov.: 31

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.266 AC: 40315 AN: 151824 Hom.: 7643 Cov.: 31 AF XY: 0.266 AC XY: 19735 AN XY: 74230

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.253

Alfa AF: 0.213 Hom.: 677

Bravo AF: 0.303

Asia WGS AF: 0.358 AC: 1238 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.25
DANN	Benign	0.83

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: rs5754227; hg19: chr22-33105817;