rs743742

Variant names:

• chr22-32720328-C-A
• rs743742
• NM_003490.4:c.712-123592G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-32720328-C-A
• chr22-32720328-C-G
• chr22-32720328-C-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.712-123592G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,150 control chromosomes in the GnomAD database, including 5,418 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 0.24 (5418 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 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.712-123592G>T		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.712-123592G>T		intron	N/A	NP_001356836.1	O14994
	SYN3	NM_001369908.1		c.712-123592G>T		intron	N/A	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.712-123592G>T		intron	N/A	ENSP00000351614.2	O14994
	SYN3	ENST00000462268.1	TSL:3	n.226-90460G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36743 AN: 152032 Hom.: 5408 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.242 AC: 36782 AN: 152150 Hom.: 5418 Cov.: 32 AF XY: 0.241 AC XY: 17958 AN XY: 74410

African (AFR) AF: 0.341 AC: 14168 AN: 41500

American (AMR) AF: 0.316 AC: 4828 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 595 AN: 3472

East Asian (EAS) AF: 0.626 AC: 3234 AN: 5166

South Asian (SAS) AF: 0.130 AC: 628 AN: 4828

European-Finnish (FIN) AF: 0.159 AC: 1680 AN: 10596

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11025 AN: 67996

Other (OTH) AF: 0.227 AC: 479 AN: 2114

Alfa AF: 0.194 Hom.: 14427

Bravo AF: 0.267

Asia WGS AF: 0.343 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.43
PhyloP100		-0.91
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: rs743742; hg19: chr22-33116314;