chr22-32688525-A-C

Variant names:

• chr22-32688525-A-C
• rs9621532
• NM_003490.4:c.712-91789T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003490.4(SYN3):​c.712-91789T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0582 in 152,176 control chromosomes in the GnomAD database, including 287 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 0.058 (287 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• Publications: 67 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.073 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.712-91789T>G		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.712-91789T>G		intron	N/A	NP_001356836.1	O14994
	SYN3	NM_001369908.1		c.712-91789T>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.712-91789T>G		intron	N/A	ENSP00000351614.2	O14994
	SYN3	ENST00000462268.1	TSL:3	n.226-58657T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0582 AC: 8846 AN: 152058 Hom.: 286 Cov.: 32

Gnomad AFR AF: 0.0754

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.0309

Gnomad SAS AF: 0.0667

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.0640

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

GnomAD4 genome AF: 0.0582 AC: 8856 AN: 152176 Hom.: 287 Cov.: 32 AF XY: 0.0579 AC XY: 4306 AN XY: 74392

African (AFR) AF: 0.0752 AC: 3120 AN: 41500

American (AMR) AF: 0.0723 AC: 1106 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3472

East Asian (EAS) AF: 0.0310 AC: 160 AN: 5166

South Asian (SAS) AF: 0.0667 AC: 321 AN: 4812

European-Finnish (FIN) AF: 0.0318 AC: 337 AN: 10606

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0495 AC: 3365 AN: 68008

Other (OTH) AF: 0.0666 AC: 141 AN: 2116

Alfa AF: 0.0649 Hom.: 129

Bravo AF: 0.0650

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.0
DANN	Benign	0.90
PhyloP100		-0.37
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: rs9621532; hg19: chr22-33084511;