rs137487

Positions:

• chr22-32863117-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003490.4(SYN3):​c.711+1798T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,450 control chromosomes in the GnomAD database, including 26,673 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 0.58 (26638 hom., cov: 32)
  • Exomes 𝑓: 0.44 (35 hom.)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.696

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN3	NM_003490.4	c.711+1798T>C		intron_variant		ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.711+1798T>C		intron_variant		5	NM_003490.4	ENSP00000351614	P1
SYN3	ENST00000462268.1	n.225+1798T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88425 AN: 151900 Hom.: 26590 Cov.: 32

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.569

GnomAD4 exome AF: 0.440 AC: 191 AN: 434 Hom.: 35 AF XY: 0.439 AC XY: 116 AN XY: 264

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.433

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.582 AC: 88521 AN: 152016 Hom.: 26638 Cov.: 32 AF XY: 0.577 AC XY: 42856 AN XY: 74302

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.565

Alfa AF: 0.528 Hom.: 21090

Bravo AF: 0.608

Asia WGS AF: 0.536 AC: 1863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs137487; hg19: chr22-33259104;