rs5749511

Positions:

• chr22-32800398-C-T

Variant summary

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

The NM_003490.4(SYN3):​c.711+64517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0501 in 152,210 control chromosomes in the GnomAD database, including 231 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 0.050 (231 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN3	NM_003490.4	c.711+64517G>A		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+64517G>A		intron_variant		5	NM_003490.4	ENSP00000351614.2
SYN3	ENST00000462268.1	n.225+64517G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7623 AN: 152092 Hom.: 231 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.0432

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

GnomAD4 genome AF: 0.0501 AC: 7630 AN: 152210 Hom.: 231 Cov.: 32 AF XY: 0.0490 AC XY: 3645 AN XY: 74424

Gnomad4 AFR AF: 0.0496

Gnomad4 AMR AF: 0.0364

Gnomad4 ASJ AF: 0.0844

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.0355

Gnomad4 FIN AF: 0.0350

Gnomad4 NFE AF: 0.0560

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.0556 Hom.: 41

Bravo AF: 0.0486

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.75

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: rs5749511; hg19: chr22-33196384;