rs133945

Positions:

• chr22-33006858-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003490.4(SYN3):​c.-162-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 511,090 control chromosomes in the GnomAD database, including 54,868 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 0.45 (15422 hom., cov: 32)
  • Exomes 𝑓: 0.46 (39446 hom.)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.91

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN3	NM_003490.4	c.-162-34G>A		intron_variant		ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.-162-34G>A		intron_variant		5	NM_003490.4	ENSP00000351614	P1
SYN3	ENST00000441821.5	c.-162-34G>A		intron_variant		1		ENSP00000395794
SYN3	ENST00000412575.1	c.-162-34G>A		intron_variant		5		ENSP00000388582

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67775 AN: 151840 Hom.: 15421 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.487

GnomAD4 exome AF: 0.463 AC: 166101 AN: 359132 Hom.: 39446 Cov.: 4 AF XY: 0.464 AC XY: 85104 AN XY: 183586

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.364

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.490

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.446 AC: 67791 AN: 151958 Hom.: 15422 Cov.: 32 AF XY: 0.446 AC XY: 33156 AN XY: 74278

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.482

Alfa AF: 0.479 Hom.: 26985

Bravo AF: 0.438

Asia WGS AF: 0.358 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.018
DANN	Benign	0.71

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: rs133945; hg19: chr22-33402843;