rs135123

Positions:

• chr22-32528746-C-G
• chr22-32528746-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003490.4(SYN3):​c.1230+128G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,346,874 control chromosomes in the GnomAD database, including 22,482 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 0.17 (2236 hom., cov: 33)
  • Exomes 𝑓: 0.18 (20246 hom.)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN3	NM_003490.4	c.1230+128G>C		intron_variant		ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.1230+128G>C		intron_variant		5	NM_003490.4	ENSP00000351614	P1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25376 AN: 152132 Hom.: 2240 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.0809

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.181 AC: 215822 AN: 1194624 Hom.: 20246 AF XY: 0.180 AC XY: 106266 AN XY: 589740

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.0814

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.167 AC: 25372 AN: 152250 Hom.: 2236 Cov.: 33 AF XY: 0.165 AC XY: 12278 AN XY: 74436

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.0811

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.177

Alfa AF: 0.0824 Hom.: 116

Bravo AF: 0.172

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.92
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -47

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs135123; hg19: chr22-32924733;