NM_003490.4:c.711+93233G>T

Variant names:

• chr22-32771682-C-A
• rs9606993
• NM_003490.4:c.711+93233G>T

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+93233G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,192 control chromosomes in the GnomAD database, including 2,273 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 0.15 (2273 hom., cov: 33)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 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.711+93233G>T		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.711+93233G>T		intron	N/A	NP_001356836.1
	SYN3	NM_001369908.1		c.711+93233G>T		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.711+93233G>T		intron	N/A	ENSP00000351614.2
	SYN3	ENST00000462268.1	TSL:3	n.225+93233G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23093 AN: 152074 Hom.: 2271 Cov.: 33

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.152 AC: 23093 AN: 152192 Hom.: 2273 Cov.: 33 AF XY: 0.158 AC XY: 11728 AN XY: 74388

African (AFR) AF: 0.0348 AC: 1446 AN: 41548

American (AMR) AF: 0.168 AC: 2563 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 388 AN: 3472

East Asian (EAS) AF: 0.350 AC: 1802 AN: 5152

South Asian (SAS) AF: 0.292 AC: 1405 AN: 4816

European-Finnish (FIN) AF: 0.222 AC: 2352 AN: 10590

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12643 AN: 68012

Other (OTH) AF: 0.166 AC: 349 AN: 2108

Alfa AF: 0.171 Hom.: 6930

Bravo AF: 0.143

Asia WGS AF: 0.294 AC: 1025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.77
PhyloP100		0.42
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: rs9606993; hg19: chr22-33167668;