chr22-32800707-T-C

Variant names:

• chr22-32800707-T-C
• rs9619311
• NM_003490.4:c.711+64208A>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.711+64208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,048 control chromosomes in the GnomAD database, including 13,424 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 0.39 (13424 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818
• Publications: 52 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 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+64208A>G		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.711+64208A>G		intron	N/A	NP_001356836.1
	SYN3	NM_001369908.1		c.711+64208A>G		intron	N/A	NP_001356837.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	ENST00000358763.7	TSL:5 MANE Select	c.711+64208A>G		intron	N/A	ENSP00000351614.2
	SYN3	ENST00000462268.1	TSL:3	n.225+64208A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59407 AN: 151930 Hom.: 13388 Cov.: 32

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.0912

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.391 AC: 59504 AN: 152048 Hom.: 13424 Cov.: 32 AF XY: 0.384 AC XY: 28543 AN XY: 74318

African (AFR) AF: 0.627 AC: 25987 AN: 41448

American (AMR) AF: 0.365 AC: 5572 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1299 AN: 3472

East Asian (EAS) AF: 0.0914 AC: 473 AN: 5176

South Asian (SAS) AF: 0.209 AC: 1008 AN: 4820

European-Finnish (FIN) AF: 0.278 AC: 2943 AN: 10572

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21078 AN: 67958

Other (OTH) AF: 0.397 AC: 839 AN: 2112

Alfa AF: 0.336 Hom.: 28584

Bravo AF: 0.413

Asia WGS AF: 0.191 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		-0.82
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: rs9619311; hg19: chr22-33196693;