22-32929818-T-G

Variant names:

• chr22-32929818-T-G
• rs10483167
• NM_003490.4:c.461+1572A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003490.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	NM_003490.4	MANE Select	c.461+1572A>C		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.461+1572A>C		intron	N/A	NP_001356836.1	O14994
	SYN3	NM_001369908.1		c.461+1572A>C		intron	N/A	NP_001356837.1	O14994

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	ENST00000358763.7	TSL:5 MANE Select	c.461+1572A>C		intron	N/A	ENSP00000351614.2	O14994

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

African (AFR) AF: 0.0691 AC: 2869 AN: 41512

American (AMR) AF: 0.213 AC: 3252 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1076 AN: 3468

East Asian (EAS) AF: 0.166 AC: 859 AN: 5162

South Asian (SAS) AF: 0.346 AC: 1666 AN: 4816

European-Finnish (FIN) AF: 0.373 AC: 3937 AN: 10550

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22834 AN: 67938

Other (OTH) AF: 0.258 AC: 544 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.77
PhyloP100		0.18
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: rs10483167; hg19: chr22-33325803;