rs9621532

Positions:

• chr22-32688525-A-C
• chr22-32688525-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003490.4(SYN3):​c.712-91789T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0582 in 152,176 control chromosomes in the GnomAD database, including 287 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 0.058 (287 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN3	NM_003490.4	c.712-91789T>G		intron_variant		ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.712-91789T>G		intron_variant		5	NM_003490.4	ENSP00000351614	P1
SYN3	ENST00000462268.1	n.226-58657T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0582 AC: 8846 AN: 152058 Hom.: 286 Cov.: 32

Gnomad AFR AF: 0.0754

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.0309

Gnomad SAS AF: 0.0667

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.0640

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

GnomAD4 genome AF: 0.0582 AC: 8856 AN: 152176 Hom.: 287 Cov.: 32 AF XY: 0.0579 AC XY: 4306 AN XY: 74392

Gnomad4 AFR AF: 0.0752

Gnomad4 AMR AF: 0.0723

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.0310

Gnomad4 SAS AF: 0.0667

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.0495

Gnomad4 OTH AF: 0.0666

Alfa AF: 0.0595 Hom.: 39

Bravo AF: 0.0650

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.0
DANN	Benign	0.90

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

Publications

LitVar

Other links and lift over

dbSNP: rs9621532; hg19: chr22-33084511;