NM_003490.4:c.-163+14142T>C

Variant names:

• chr22-33044150-A-G
• rs5998705
• NM_003490.4:c.-163+14142T>C

Variant summary

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

The NM_003490.4(SYN3):​c.-163+14142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,052 control chromosomes in the GnomAD database, including 7,235 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 0.28 (7235 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 5 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]

ENSG00000300892 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	NM_003490.4	MANE Select	c.-163+14142T>C		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.-160+14142T>C		intron	N/A	NP_001356836.1
	SYN3	NM_001369908.1		c.-163+8075T>C		intron	N/A	NP_001356837.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	ENST00000358763.7	TSL:5 MANE Select	c.-163+14142T>C		intron	N/A	ENSP00000351614.2
	SYN3	ENST00000441821.5	TSL:1	c.-163+13385T>C		intron	N/A	ENSP00000395794.1
	ENSG00000300892	ENST00000774864.1		n.315+8075T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42637 AN: 151936 Hom.: 7228 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.281 AC: 42686 AN: 152052 Hom.: 7235 Cov.: 32 AF XY: 0.280 AC XY: 20802 AN XY: 74328

African (AFR) AF: 0.440 AC: 18219 AN: 41448

American (AMR) AF: 0.350 AC: 5351 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 863 AN: 3466

East Asian (EAS) AF: 0.514 AC: 2646 AN: 5146

South Asian (SAS) AF: 0.211 AC: 1018 AN: 4822

European-Finnish (FIN) AF: 0.139 AC: 1470 AN: 10578

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12399 AN: 67988

Other (OTH) AF: 0.263 AC: 555 AN: 2112

Alfa AF: 0.218 Hom.: 8808

Bravo AF: 0.306

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.5
DANN	Benign	0.57
PhyloP100		0.11
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: rs5998705; hg19: chr22-33440135;