rs574127377

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003490.4(SYN3):c.1547G>T(p.Gly516Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000158 in 1,584,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SYN3
NM_003490.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.43

Publications

0 publications found

Variant links:

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]

SYN3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.122826874).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYN3	NM_003490.4	MANE Select	c.1547G>T	p.Gly516Val	missense	Exon 13 of 14	NP_003481.3
SYN3	NM_001369907.1		c.1547G>T	p.Gly516Val	missense	Exon 13 of 14	NP_001356836.1	O14994
SYN3	NM_001369908.1		c.1547G>T	p.Gly516Val	missense	Exon 13 of 14	NP_001356837.1	O14994

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYN3	ENST00000358763.7	TSL:5 MANE Select	c.1547G>T	p.Gly516Val	missense	Exon 13 of 14	ENSP00000351614.2	O14994
SYN3	ENST00000459990.5	TSL:4	n.520G>T		non_coding_transcript_exon	Exon 3 of 3
SYN3	ENST00000461446.1	TSL:2	n.438G>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.0000133

AC:

AN:

225086

AF XY:

0.00000829

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000169

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000147

AC:

AN:

1432426

Hom.:

Cov.:

AF XY:

0.0000169

AC XY:

AN XY:

709874

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32702

American (AMR)

AF:

0.00

AC:

AN:

40862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23854

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39476

South Asian (SAS)

AF:

0.00

AC:

AN:

80460

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098066

Other (OTH)

AF:

0.000338

AC:

AN:

59142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41560

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

M_CAP

Benign

0.016

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

5.4

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.086

Sift

Uncertain

0.012

Sift4G

Uncertain

0.044

Polyphen

0.75

Vest4

0.45

MutPred

0.22

Loss of relative solvent accessibility (P = 0.0676)

MVP

0.17

MPC

0.84

ClinPred

0.54

GERP RS

4.9

Varity_R

0.21

gMVP

0.27

Mutation Taster

=61/39

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over