NM_003490.4:c.711+125191C>G

Variant names:

• chr22-32739724-G-C
• rs762883
• NM_003490.4:c.711+125191C>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.711+125191C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 152,038 control chromosomes in the GnomAD database, including 20,119 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 0.51 (20119 hom., cov: 33)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.711+125191C>G		intron_variant	Intron 6 of 13	ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.711+125191C>G		intron_variant	Intron 6 of 13	5	NM_003490.4	ENSP00000351614.2
SYN3	ENST00000462268.1	n.226-109856C>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77057 AN: 151920 Hom.: 20085 Cov.: 33

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.507 AC: 77145 AN: 152038 Hom.: 20119 Cov.: 33 AF XY: 0.512 AC XY: 38049 AN XY: 74320

African (AFR) AF: 0.520 AC: 21562 AN: 41450

American (AMR) AF: 0.590 AC: 9024 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1410 AN: 3468

East Asian (EAS) AF: 0.876 AC: 4537 AN: 5178

South Asian (SAS) AF: 0.533 AC: 2569 AN: 4818

European-Finnish (FIN) AF: 0.473 AC: 4988 AN: 10552

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.462 AC: 31371 AN: 67974

Other (OTH) AF: 0.516 AC: 1089 AN: 2110

Alfa AF: 0.481 Hom.: 2194

Bravo AF: 0.525

Asia WGS AF: 0.670 AC: 2331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.9
DANN	Benign	0.71
PhyloP100		-0.023
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: rs762883; hg19: chr22-33135710;