22-32712072-G-C

Variant names:

• chr22-32712072-G-C
• rs7291198
• NM_003490.4:c.712-115336C>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.712-115336C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,032 control chromosomes in the GnomAD database, including 7,539 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 0.25 (7539 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.712-115336C>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.712-115336C>G		intron_variant	Intron 6 of 13	5	NM_003490.4	ENSP00000351614.2
SYN3	ENST00000462268.1	n.226-82204C>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37793 AN: 151914 Hom.: 7517 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.0856

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.249 AC: 37863 AN: 152032 Hom.: 7539 Cov.: 32 AF XY: 0.250 AC XY: 18566 AN XY: 74314

African (AFR) AF: 0.508 AC: 21063 AN: 41434

American (AMR) AF: 0.284 AC: 4339 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3466

East Asian (EAS) AF: 0.632 AC: 3252 AN: 5148

South Asian (SAS) AF: 0.0851 AC: 410 AN: 4820

European-Finnish (FIN) AF: 0.112 AC: 1185 AN: 10596

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0978 AC: 6652 AN: 67992

Other (OTH) AF: 0.212 AC: 445 AN: 2104

Alfa AF: 0.0513 Hom.: 58

Bravo AF: 0.283

Asia WGS AF: 0.333 AC: 1159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.69
DANN	Benign	0.68
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: rs7291198; hg19: chr22-33108058;