NM_003490.4:c.712-63619A>G

Variant names:

• chr22-32660355-T-C
• rs4821083
• NM_003490.4:c.712-63619A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003490.4(SYN3):​c.712-63619A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,078 control chromosomes in the GnomAD database, including 7,128 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 0.26 (7128 hom., cov: 33)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.633
• Publications: 30 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]

LOC105373002 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.712-63619A>G		intron_variant	Intron 6 of 13	ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.712-63619A>G		intron_variant	Intron 6 of 13	5	NM_003490.4	ENSP00000351614.2
SYN3	ENST00000462268.1	n.226-30487A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40163 AN: 151958 Hom.: 7110 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.265 AC: 40233 AN: 152078 Hom.: 7128 Cov.: 33 AF XY: 0.266 AC XY: 19780 AN XY: 74350

African (AFR) AF: 0.423 AC: 17507 AN: 41412

American (AMR) AF: 0.357 AC: 5459 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3472

East Asian (EAS) AF: 0.714 AC: 3679 AN: 5156

South Asian (SAS) AF: 0.173 AC: 835 AN: 4818

European-Finnish (FIN) AF: 0.137 AC: 1448 AN: 10596

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10094 AN: 68010

Other (OTH) AF: 0.256 AC: 541 AN: 2116

Alfa AF: 0.192 Hom.: 7590

Bravo AF: 0.300

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.32
PhyloP100		-0.63
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: rs4821083; hg19: chr22-33056341;