rs137515

Variant names:

• chr22-32893765-C-T
• rs137515
• NM_003490.4:c.462-24640G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003490.4(SYN3):​c.462-24640G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,674 control chromosomes in the GnomAD database, including 19,507 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 0.50 (19507 hom., cov: 30)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.462-24640G>A		intron_variant	Intron 4 of 13	ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.462-24640G>A		intron_variant	Intron 4 of 13	5	NM_003490.4	ENSP00000351614.2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75348 AN: 151556 Hom.: 19501 Cov.: 30

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.497 AC: 75378 AN: 151674 Hom.: 19507 Cov.: 30 AF XY: 0.490 AC XY: 36292 AN XY: 74056

African (AFR) AF: 0.422 AC: 17470 AN: 41366

American (AMR) AF: 0.438 AC: 6686 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1827 AN: 3470

East Asian (EAS) AF: 0.144 AC: 737 AN: 5108

South Asian (SAS) AF: 0.344 AC: 1654 AN: 4802

European-Finnish (FIN) AF: 0.615 AC: 6440 AN: 10470

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.573 AC: 38883 AN: 67898

Other (OTH) AF: 0.482 AC: 1015 AN: 2106

Alfa AF: 0.533 Hom.: 5207

Bravo AF: 0.483

Asia WGS AF: 0.258 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	0.78
PhyloP100		0.52
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: rs137515; hg19: chr22-33289751;