22-32518325-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003490.4(SYN3):c.1328G>A(p.Arg443His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00619 in 1,607,586 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 32 hom. )

Consequence

SYN3
NM_003490.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.25

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006853074).

BP6

Variant 22-32518325-C-T is Benign according to our data. Variant chr22-32518325-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 785839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4 link	c.1328G>A	p.Arg443His	missense_variant	Exon 13 of 14	ENST00000358763.7	NP_003481.3	O14994A0A024R1I8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7 link	c.1328G>A	p.Arg443His	missense_variant	Exon 13 of 14	5	NM_003490.4	ENSP00000351614.2		O14994

Frequencies

GnomAD3 genomes

AF:

0.00555

AC:

842

AN:

151616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00479

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00354

Gnomad FIN

AF:

0.00743

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00822

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00577

AC:

1401

AN:

242826

AF XY:

0.00600

show subpopulations

Gnomad AFR exome

AF:

0.00147

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.0000550

Gnomad FIN exome

AF:

0.00687

Gnomad NFE exome

AF:

0.00755

Gnomad OTH exome

AF:

0.00642

GnomAD4 exome

AF:

0.00625

AC:

9102

AN:

1455856

Hom.:

Cov.:

AF XY:

0.00636

AC XY:

4603

AN XY:

723824

show subpopulations

African (AFR)

AF:

0.000905

AC:

AN:

33144

American (AMR)

AF:

0.00298

AC:

131

AN:

43946

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

289

AN:

25780

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39660

South Asian (SAS)

AF:

0.00532

AC:

454

AN:

85358

European-Finnish (FIN)

AF:

0.00627

AC:

332

AN:

52988

Middle Eastern (MID)

AF:

0.00749

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00669

AC:

7422

AN:

1109160

Other (OTH)

AF:

0.00664

AC:

399

AN:

60078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

497

993

1490

1986

2483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00556

AC:

843

AN:

151730

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

427

AN XY:

74114

show subpopulations

African (AFR)

AF:

0.00143

AC:

AN:

41360

American (AMR)

AF:

0.00479

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3460

East Asian (EAS)

AF:

0.000388

AC:

AN:

5150

South Asian (SAS)

AF:

0.00376

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00743

AC:

AN:

10496

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00822

AC:

558

AN:

67910

Other (OTH)

AF:

0.00758

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

122

163

204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00772

Hom.:

Bravo

AF:

0.00487

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.00589

AC:

715

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SYN3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.0087

MetaRNN

Benign

0.0069

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;.

PhyloP100

3.3

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.5

N;.

REVEL

Benign

0.094

Sift

Benign

0.073

T;.

Sift4G

Benign

0.12

T;T

Polyphen

1.0

D;.

Vest4

0.52

MVP

0.32

MPC

0.24

ClinPred

0.0091

GERP RS

4.6

Varity_R

0.13

gMVP

0.15

Mutation Taster

=96/4

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

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22-32518325-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over