22-32511734-G-C

Variant names:

• chr22-32511734-G-C
• rs1894450
• NM_003490.4:c.*1958C>G

Variant summary

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

The NM_003490.4(SYN3):​c.*1958C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,154 control chromosomes in the GnomAD database, including 23,106 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 0.50 (23106 hom., cov: 33)
• Consequence: SYN3 NM_003490.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 7 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 = 0.877 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	NM_003490.4	MANE Select	c.*1958C>G		3_prime_UTR	Exon 14 of 14	NP_003481.3
	SYN3	NM_001369907.1		c.*1958C>G		3_prime_UTR	Exon 14 of 14	NP_001356836.1
	SYN3	NM_001369908.1		c.*1958C>G		3_prime_UTR	Exon 14 of 14	NP_001356837.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	ENST00000358763.7	TSL:5 MANE Select	c.*1958C>G		3_prime_UTR	Exon 14 of 14	ENSP00000351614.2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75409 AN: 152036 Hom.: 23109 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.496 AC: 75413 AN: 152154 Hom.: 23106 Cov.: 33 AF XY: 0.510 AC XY: 37932 AN XY: 74382

African (AFR) AF: 0.125 AC: 5182 AN: 41522

American (AMR) AF: 0.593 AC: 9062 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2514 AN: 3472

East Asian (EAS) AF: 0.898 AC: 4647 AN: 5172

South Asian (SAS) AF: 0.770 AC: 3717 AN: 4828

European-Finnish (FIN) AF: 0.696 AC: 7372 AN: 10592

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.604 AC: 41036 AN: 67966

Other (OTH) AF: 0.535 AC: 1128 AN: 2110

Alfa AF: 0.403 Hom.: 1293

Bravo AF: 0.470

Asia WGS AF: 0.741 AC: 2574 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	5.6
DANN	Benign	0.65
PhyloP100		1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1894450; hg19: chr22-32907721;