rs9609656

Variant names:

• chr22-32920295-C-T
• rs9609656
• NM_003490.4:c.461+11095G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003490.4(SYN3):​c.461+11095G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,182 control chromosomes in the GnomAD database, including 1,897 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 0.13 (1897 hom., cov: 33)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 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.461+11095G>A		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.461+11095G>A		intron	N/A	NP_001356836.1	O14994
	SYN3	NM_001369908.1		c.461+11095G>A		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.461+11095G>A		intron	N/A	ENSP00000351614.2	O14994

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20226 AN: 152064 Hom.: 1898 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.0645

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.133 AC: 20233 AN: 152182 Hom.: 1897 Cov.: 33 AF XY: 0.136 AC XY: 10106 AN XY: 74420

African (AFR) AF: 0.151 AC: 6258 AN: 41508

American (AMR) AF: 0.223 AC: 3414 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0645 AC: 224 AN: 3472

East Asian (EAS) AF: 0.459 AC: 2364 AN: 5154

South Asian (SAS) AF: 0.127 AC: 610 AN: 4822

European-Finnish (FIN) AF: 0.0747 AC: 793 AN: 10616

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0921 AC: 6265 AN: 68010

Other (OTH) AF: 0.114 AC: 241 AN: 2106

Alfa AF: 0.106 Hom.: 637

Bravo AF: 0.146

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.64
PhyloP100		-0.041
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: rs9609656; hg19: chr22-33316280;