rs9606994

Variant names:

• chr22-32797064-G-A
• rs9606994
• NM_003490.4:c.711+67851C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-32797064-G-A
• chr22-32797064-G-T

Variant summary

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

The NM_003490.4(SYN3):​c.711+67851C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,840 control chromosomes in the GnomAD database, including 12,809 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 0.40 (12809 hom., cov: 31)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 8 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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.711+67851C>T		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.711+67851C>T		intron_variant	Intron 6 of 13	5	NM_003490.4	ENSP00000351614.2
SYN3	ENST00000462268.1	n.225+67851C>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61176 AN: 151720 Hom.: 12811 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.403 AC: 61190 AN: 151840 Hom.: 12809 Cov.: 31 AF XY: 0.406 AC XY: 30081 AN XY: 74178

African (AFR) AF: 0.289 AC: 11981 AN: 41418

American (AMR) AF: 0.434 AC: 6623 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3470

East Asian (EAS) AF: 0.547 AC: 2789 AN: 5096

South Asian (SAS) AF: 0.457 AC: 2193 AN: 4800

European-Finnish (FIN) AF: 0.453 AC: 4772 AN: 10542

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.442 AC: 30027 AN: 67932

Other (OTH) AF: 0.391 AC: 824 AN: 2108

Alfa AF: 0.374 Hom.: 2426

Bravo AF: 0.393

Asia WGS AF: 0.483 AC: 1675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.9
DANN	Benign	0.91
PhyloP100		0.021
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: rs9606994; hg19: chr22-33193050;