22-32512751-T-C

Variant names:

• chr22-32512751-T-C
• rs1056484
• NM_003490.4:c.*941A>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.*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
• Publications: 10 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003490.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	NM_003490.4	MANE Select	c.*941A>G		3_prime_UTR	Exon 14 of 14	NP_003481.3
	SYN3	NM_001369907.1		c.*941A>G		3_prime_UTR	Exon 14 of 14	NP_001356836.1	O14994
	SYN3	NM_001369908.1		c.*941A>G		3_prime_UTR	Exon 14 of 14	NP_001356837.1	O14994

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	ENST00000358763.7	TSL:5 MANE Select	c.*941A>G		3_prime_UTR	Exon 14 of 14	ENSP00000351614.2	O14994

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.126 AC: 5238 AN: 41520

American (AMR) AF: 0.642 AC: 9806 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2486 AN: 3470

East Asian (EAS) AF: 0.914 AC: 4731 AN: 5176

South Asian (SAS) AF: 0.771 AC: 3713 AN: 4816

European-Finnish (FIN) AF: 0.695 AC: 7344 AN: 10570

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41081 AN: 67958

Other (OTH) AF: 0.541 AC: 1143 AN: 2112

Alfa AF: 0.570 Hom.: 34770

Bravo AF: 0.481

Asia WGS AF: 0.752 AC: 2614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.36
PhyloP100		0.34
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: rs1056484; hg19: chr22-32908738;