chr22-32512751-T-C

Position:

• chr22-32512751-T-C

Variant summary

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

The NM_003490.4(SYN3):​c.*941A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,118 control chromosomes in the GnomAD database, including 23,680 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 0.50 (23678 hom., cov: 32)
  • Exomes 𝑓: 0.83 (2 hom.)
• Consequence: SYN3 NM_003490.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYN3	NM_003490.4	c.*941A>G		3_prime_UTR_variant	14/14	ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.*941A>G		3_prime_UTR_variant	14/14	5	NM_003490.4	ENSP00000351614	P1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76291 AN: 151990 Hom.: 23677 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.541

GnomAD4 exome AF: 0.833 AC: 5 AN: 6 Hom.: 2 Cov.: 0 AF XY: 0.833 AC XY: 5 AN XY: 6

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.502 AC: 76299 AN: 152112 Hom.: 23678 Cov.: 32 AF XY: 0.517 AC XY: 38417 AN XY: 74336

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.541

Alfa AF: 0.584 Hom.: 27955

Bravo AF: 0.481

Asia WGS AF: 0.752 AC: 2614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.36

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: rs1056484; hg19: chr22-32908738;