NM_003490.4:c.774+3519A>T

Variant names:

• chr22-32593155-T-A
• rs2858723
• NM_003490.4:c.774+3519A>T

Variant summary

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

The NM_003490.4(SYN3):​c.774+3519A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,166 control chromosomes in the GnomAD database, including 2,268 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 0.11 (2268 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556
• Publications: 2 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 (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.774+3519A>T		intron_variant	Intron 7 of 13	ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.774+3519A>T		intron_variant	Intron 7 of 13	5	NM_003490.4	ENSP00000351614.2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17128 AN: 152048 Hom.: 2263 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0526

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.113 AC: 17165 AN: 152166 Hom.: 2268 Cov.: 32 AF XY: 0.110 AC XY: 8209 AN XY: 74438

African (AFR) AF: 0.317 AC: 13139 AN: 41436

American (AMR) AF: 0.0526 AC: 805 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3470

East Asian (EAS) AF: 0.119 AC: 619 AN: 5180

South Asian (SAS) AF: 0.0365 AC: 176 AN: 4818

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10618

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0262 AC: 1785 AN: 68024

Other (OTH) AF: 0.102 AC: 215 AN: 2114

Alfa AF: 0.0218 Hom.: 50

Bravo AF: 0.127

Asia WGS AF: 0.0940 AC: 328 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	6.6
DANN	Benign	0.31
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2858723; hg19: chr22-32989141;