22-32866948-T-C

Variant names:

• chr22-32866948-T-C
• rs137489
• NM_003490.4:c.622-1944A>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.622-1944A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,128 control chromosomes in the GnomAD database, including 4,550 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 0.23 (4550 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 11 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 = 0.487 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.622-1944A>G		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.622-1944A>G		intron	N/A	NP_001356836.1
	SYN3	NM_001369908.1		c.622-1944A>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.622-1944A>G		intron	N/A	ENSP00000351614.2
	SYN3	ENST00000462268.1	TSL:3	n.136-1944A>G		intron	N/A
	SYN3	ENST00000467824.1	TSL:3	n.94-1944A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35184 AN: 152012 Hom.: 4547 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.231 AC: 35179 AN: 152128 Hom.: 4550 Cov.: 32 AF XY: 0.234 AC XY: 17371 AN XY: 74362

African (AFR) AF: 0.171 AC: 7086 AN: 41498

American (AMR) AF: 0.367 AC: 5616 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3472

East Asian (EAS) AF: 0.503 AC: 2597 AN: 5166

South Asian (SAS) AF: 0.170 AC: 819 AN: 4818

European-Finnish (FIN) AF: 0.175 AC: 1860 AN: 10606

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15519 AN: 67964

Other (OTH) AF: 0.239 AC: 504 AN: 2112

Alfa AF: 0.233 Hom.: 13856

Bravo AF: 0.247

Asia WGS AF: 0.351 AC: 1217 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	4.8
DANN	Benign	0.58
PhyloP100		1.8
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: rs137489; hg19: chr22-33262935;