22-32796558-C-T

Variant names:

• chr22-32796558-C-T
• rs5754289
• NM_003490.4:c.711+68357G>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.711+68357G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,072 control chromosomes in the GnomAD database, including 6,047 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 0.25 (6047 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 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.711+68357G>A		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.711+68357G>A		intron	N/A	NP_001356836.1	O14994
	SYN3	NM_001369908.1		c.711+68357G>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.711+68357G>A		intron	N/A	ENSP00000351614.2	O14994
	SYN3	ENST00000462268.1	TSL:3	n.225+68357G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38281 AN: 151954 Hom.: 6027 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.252 AC: 38353 AN: 152072 Hom.: 6047 Cov.: 32 AF XY: 0.247 AC XY: 18367 AN XY: 74338

African (AFR) AF: 0.453 AC: 18788 AN: 41444

American (AMR) AF: 0.180 AC: 2749 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3468

East Asian (EAS) AF: 0.0600 AC: 310 AN: 5170

South Asian (SAS) AF: 0.169 AC: 813 AN: 4810

European-Finnish (FIN) AF: 0.176 AC: 1862 AN: 10592

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12411 AN: 67990

Other (OTH) AF: 0.247 AC: 522 AN: 2112

Alfa AF: 0.203 Hom.: 12566

Bravo AF: 0.262

Asia WGS AF: 0.139 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.25
DANN	Benign	0.31
PhyloP100		-0.72
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: rs5754289; hg19: chr22-33192544;