22-32784090-A-G

Variant names:

• chr22-32784090-A-G
• rs5749509
• NM_003490.4:c.711+80825T>C

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+80825T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,146 control chromosomes in the GnomAD database, including 5,681 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 0.26 (5681 hom., cov: 33)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• 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]

ENSG00000229673 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.711+80825T>C		intron_variant	Intron 6 of 13	ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.711+80825T>C		intron_variant	Intron 6 of 13	5	NM_003490.4	ENSP00000351614.2
ENSG00000229673	ENST00000444982.1	n.62-807A>G		intron_variant	Intron 1 of 1	3
SYN3	ENST00000462268.1	n.225+80825T>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39523 AN: 152028 Hom.: 5670 Cov.: 33

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0563

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.260 AC: 39578 AN: 152146 Hom.: 5681 Cov.: 33 AF XY: 0.255 AC XY: 18973 AN XY: 74404

African (AFR) AF: 0.393 AC: 16290 AN: 41474

American (AMR) AF: 0.271 AC: 4141 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 773 AN: 3472

East Asian (EAS) AF: 0.0562 AC: 291 AN: 5178

South Asian (SAS) AF: 0.140 AC: 673 AN: 4824

European-Finnish (FIN) AF: 0.182 AC: 1931 AN: 10586

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14732 AN: 67996

Other (OTH) AF: 0.262 AC: 553 AN: 2114

Alfa AF: 0.213 Hom.: 1454

Bravo AF: 0.276

Asia WGS AF: 0.125 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.63
DANN	Benign	0.65
PhyloP100		-0.35
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: rs5749509; hg19: chr22-33180076;