rs10483169

Variant names:

• chr22-33053432-A-G
• rs10483169
• NM_003490.4:c.-163+4860T>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+4860T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 152,246 control chromosomes in the GnomAD database, including 216 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 0.032 (216 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565
• Publications: 1 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 = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.-163+4860T>C		intron_variant	Intron 1 of 13	ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.-163+4860T>C		intron_variant	Intron 1 of 13	5	NM_003490.4	ENSP00000351614.2
SYN3	ENST00000441821.5	c.-163+4103T>C		intron_variant	Intron 1 of 2	1		ENSP00000395794.1

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4940 AN: 152128 Hom.: 215 Cov.: 32

Gnomad AFR AF: 0.00558

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.0457

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0192

Gnomad OTH AF: 0.0320

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

GnomAD4 genome AF: 0.0325 AC: 4942 AN: 152246 Hom.: 216 Cov.: 32 AF XY: 0.0369 AC XY: 2749 AN XY: 74434

African (AFR) AF: 0.00556 AC: 231 AN: 41550

American (AMR) AF: 0.125 AC: 1909 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3470

East Asian (EAS) AF: 0.129 AC: 667 AN: 5186

South Asian (SAS) AF: 0.0358 AC: 173 AN: 4826

European-Finnish (FIN) AF: 0.0457 AC: 484 AN: 10600

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0192 AC: 1306 AN: 68018

Other (OTH) AF: 0.0312 AC: 66 AN: 2116

Alfa AF: 0.0233 Hom.: 18

Bravo AF: 0.0375

Asia WGS AF: 0.0690 AC: 240 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	1.6
DANN	Benign	0.75
PhyloP100		-0.56
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: rs10483169; hg19: chr22-33449418;