rs5754227

Variant names:

• chr22-32709831-T-C
• rs5754227
• NM_003490.4:c.712-113095A>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.712-113095A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,824 control chromosomes in the GnomAD database, including 7,643 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 0.27 (7643 hom., cov: 31)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 19 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.712-113095A>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.712-113095A>G		intron_variant	Intron 6 of 13	5	NM_003490.4	ENSP00000351614.2
SYN3	ENST00000462268.1	n.226-79963A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40259 AN: 151704 Hom.: 7624 Cov.: 31

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.266 AC: 40315 AN: 151824 Hom.: 7643 Cov.: 31 AF XY: 0.266 AC XY: 19735 AN XY: 74230

African (AFR) AF: 0.489 AC: 20227 AN: 41356

American (AMR) AF: 0.334 AC: 5098 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3470

East Asian (EAS) AF: 0.629 AC: 3225 AN: 5124

South Asian (SAS) AF: 0.143 AC: 689 AN: 4814

European-Finnish (FIN) AF: 0.109 AC: 1155 AN: 10560

Middle Eastern (MID) AF: 0.159 AC: 46 AN: 290

European-Non Finnish (NFE) AF: 0.128 AC: 8717 AN: 67922

Other (OTH) AF: 0.253 AC: 534 AN: 2112

Alfa AF: 0.205 Hom.: 7129

Bravo AF: 0.303

Asia WGS AF: 0.358 AC: 1238 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.25
DANN	Benign	0.83
PhyloP100		-1.0
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: rs5754227; hg19: chr22-33105817;