chr22-32684767-T-C

Variant names:

• chr22-32684767-T-C
• rs1159220
• NM_003490.4:c.712-88031A>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.712-88031A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,046 control chromosomes in the GnomAD database, including 28,563 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 0.61 (28563 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436
• Publications: 2 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.712-88031A>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.712-88031A>G		intron_variant	Intron 6 of 13	5	NM_003490.4	ENSP00000351614.2
SYN3	ENST00000462268.1	n.226-54899A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92943 AN: 151928 Hom.: 28548 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.612 AC: 93008 AN: 152046 Hom.: 28563 Cov.: 32 AF XY: 0.609 AC XY: 45270 AN XY: 74322

African (AFR) AF: 0.641 AC: 26562 AN: 41470

American (AMR) AF: 0.663 AC: 10139 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2143 AN: 3468

East Asian (EAS) AF: 0.682 AC: 3515 AN: 5154

South Asian (SAS) AF: 0.495 AC: 2389 AN: 4822

European-Finnish (FIN) AF: 0.576 AC: 6093 AN: 10572

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40207 AN: 67958

Other (OTH) AF: 0.618 AC: 1306 AN: 2114

Alfa AF: 0.595 Hom.: 13976

Bravo AF: 0.626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism

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: rs1159220; hg19: chr22-33080753;