chr22-32929818-T-G

Position:

• chr22-32929818-T-G

Variant summary

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

The NM_003490.4(SYN3):​c.461+1572A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,028 control chromosomes in the GnomAD database, including 5,737 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 0.25 (5737 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN3	NM_003490.4	c.461+1572A>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.461+1572A>C		intron_variant		5	NM_003490.4	ENSP00000351614	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37365 AN: 151910 Hom.: 5736 Cov.: 32

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.246 AC: 37366 AN: 152028 Hom.: 5737 Cov.: 32 AF XY: 0.248 AC XY: 18405 AN XY: 74300

Gnomad4 AFR AF: 0.0691

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.258

Alfa AF: 0.177 Hom.: 601

Bravo AF: 0.223

Asia WGS AF: 0.249 AC: 867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.77

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: rs10483167; hg19: chr22-33325803;