rs5754221

Variant names:

• chr22-32707469-T-C
• rs5754221
• NM_003490.4:c.712-110733A>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.712-110733A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 152,236 control chromosomes in the GnomAD database, including 424 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 0.068 (424 hom., cov: 33)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.05
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.712-110733A>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.712-110733A>G		intron_variant	Intron 6 of 13	5	NM_003490.4	ENSP00000351614.2
SYN3	ENST00000462268.1	n.226-77601A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0682 AC: 10369 AN: 152116 Hom.: 422 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.0842

Gnomad EAS AF: 0.0313

Gnomad SAS AF: 0.0678

Gnomad FIN AF: 0.0305

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0502

Gnomad OTH AF: 0.0707

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

GnomAD4 genome AF: 0.0682 AC: 10386 AN: 152236 Hom.: 424 Cov.: 33 AF XY: 0.0674 AC XY: 5020 AN XY: 74430

African (AFR) AF: 0.111 AC: 4628 AN: 41530

American (AMR) AF: 0.0689 AC: 1054 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0842 AC: 292 AN: 3468

East Asian (EAS) AF: 0.0316 AC: 163 AN: 5164

South Asian (SAS) AF: 0.0679 AC: 328 AN: 4832

European-Finnish (FIN) AF: 0.0305 AC: 324 AN: 10618

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0502 AC: 3417 AN: 68016

Other (OTH) AF: 0.0728 AC: 154 AN: 2114

Alfa AF: 0.0535 Hom.: 430

Bravo AF: 0.0758

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0010
DANN	Benign	0.36
PhyloP100		-5.0
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: rs5754221; hg19: chr22-33103455;