22-32661638-A-C

Variant names:

• chr22-32661638-A-C
• rs3788477
• NM_003490.4:c.712-64902T>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.712-64902T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,194 control chromosomes in the GnomAD database, including 1,045 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 0.11 (1045 hom., cov: 33)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.793
• Publications: 4 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]

LOC105373002 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 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.712-64902T>G		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.712-64902T>G		intron	N/A	NP_001356836.1
	SYN3	NM_001369908.1		c.712-64902T>G		intron	N/A	NP_001356837.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	ENST00000358763.7	TSL:5 MANE Select	c.712-64902T>G		intron	N/A	ENSP00000351614.2
	SYN3	ENST00000462268.1	TSL:3	n.226-31770T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17403 AN: 152076 Hom.: 1050 Cov.: 33

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.114 AC: 17402 AN: 152194 Hom.: 1045 Cov.: 33 AF XY: 0.115 AC XY: 8534 AN XY: 74398

African (AFR) AF: 0.0837 AC: 3477 AN: 41554

American (AMR) AF: 0.103 AC: 1571 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3468

East Asian (EAS) AF: 0.203 AC: 1045 AN: 5148

South Asian (SAS) AF: 0.222 AC: 1074 AN: 4828

European-Finnish (FIN) AF: 0.0982 AC: 1041 AN: 10596

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8377 AN: 67982

Other (OTH) AF: 0.115 AC: 243 AN: 2112

Alfa AF: 0.121 Hom.: 1145

Bravo AF: 0.109

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.48
PhyloP100		0.79
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: rs3788477; hg19: chr22-33057624;