rs4447

Variant names:

• chr22-32879153-C-T
• rs4447
• NM_003490.4:c.462-10028G>A

Variant summary

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

The NM_003490.4(SYN3):​c.462-10028G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,280 control chromosomes in the GnomAD database, including 59,422 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 0.88 (59422 hom., cov: 33)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.462-10028G>A		intron_variant	Intron 4 of 13	ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.462-10028G>A		intron_variant	Intron 4 of 13	5	NM_003490.4	ENSP00000351614.2

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134347 AN: 152162 Hom.: 59365 Cov.: 33

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.883 AC: 134464 AN: 152280 Hom.: 59422 Cov.: 33 AF XY: 0.884 AC XY: 65837 AN XY: 74468

African (AFR) AF: 0.858 AC: 35641 AN: 41542

American (AMR) AF: 0.892 AC: 13653 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2804 AN: 3472

East Asian (EAS) AF: 0.893 AC: 4627 AN: 5182

South Asian (SAS) AF: 0.880 AC: 4243 AN: 4820

European-Finnish (FIN) AF: 0.928 AC: 9850 AN: 10612

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.893 AC: 60725 AN: 68024

Other (OTH) AF: 0.856 AC: 1811 AN: 2116

Alfa AF: 0.891 Hom.: 33552

Bravo AF: 0.878

Asia WGS AF: 0.907 AC: 3153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.23
PhyloP100		-1.3
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: rs4447; hg19: chr22-33275140;