rs61750217

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000433931.7(SYNJ1):c.4358G>A(p.Gly1453Glu) variant causes a missense change. The variant allele was found at a frequency of 0.013 in 1,614,048 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 15 hom., cov: 33)

Exomes 𝑓: 0.013 ( 163 hom. )

Consequence

SYNJ1
ENST00000433931.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.38

Publications

10 publications found

Variant links:

Genes affected

SYNJ1 (HGNC:11503): (synaptojanin 1) This gene encodes a phosphoinositide phosphatase that regulates levels of membrane phosphatidylinositol-4,5-bisphosphate. As such, expression of this enzyme may affect synaptic transmission and membrane trafficking. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

SYNJ1 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 53
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
early-onset Parkinson disease 20
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
atypical juvenile parkinsonism
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
young-onset Parkinson disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SYNJ1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007054746).

BP6

Variant 21-32631476-C-T is Benign according to our data. Variant chr21-32631476-C-T is described in ClinVar as Benign. ClinVar VariationId is 478356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00983 (1497/152242) while in subpopulation SAS AF = 0.017 (82/4818). AF 95% confidence interval is 0.0141. There are 15 homozygotes in GnomAd4. There are 725 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ1	NM_203446.3 link	c.*329G>A		3_prime_UTR_variant	Exon 33 of 33	ENST00000674351.1	NP_982271.3	O43426-2C9JFZ1Q05CZ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNJ1	ENST00000674351.1 link	c.*329G>A		3_prime_UTR_variant	Exon 33 of 33		NM_203446.3	ENSP00000501530.1		O43426-2

Frequencies

GnomAD3 genomes

AF:

0.00985

AC:

1499

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00956

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.00642

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0144

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0127

AC:

3187

AN:

251122

AF XY:

0.0143

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00571

Gnomad ASJ exome

AF:

0.0162

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00634

Gnomad NFE exome

AF:

0.0161

Gnomad OTH exome

AF:

0.0160

GnomAD4 exome

AF:

0.0133

AC:

19489

AN:

1461806

Hom.:

163

Cov.:

AF XY:

0.0140

AC XY:

10212

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.00284

AC:

AN:

33480

American (AMR)

AF:

0.00691

AC:

309

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0157

AC:

411

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0236

AC:

2032

AN:

86248

European-Finnish (FIN)

AF:

0.00627

AC:

335

AN:

53402

Middle Eastern (MID)

AF:

0.0477

AC:

275

AN:

5768

European-Non Finnish (NFE)

AF:

0.0137

AC:

15179

AN:

1111962

Other (OTH)

AF:

0.0141

AC:

852

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1227

2455

3682

4910

6137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.00983

AC:

1497

AN:

152242

Hom.:

Cov.:

AF XY:

0.00974

AC XY:

725

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00253

AC:

105

AN:

41536

American (AMR)

AF:

0.00955

AC:

146

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.0170

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00642

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0144

AC:

977

AN:

68034

Other (OTH)

AF:

0.0152

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

156

234

312

390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0133

Hom.:

Bravo

AF:

0.00989

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0138

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0136

AC:

117

ExAC

AF:

0.0137

AC:

1661

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0152

EpiControl

AF:

0.0163

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 11, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 03, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23804577) -

Early-onset Parkinson disease 20;C4479313:Developmental and epileptic encephalopathy, 53

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

.;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

D;D

MetaRNN

Benign

0.0071

T;T

MetaSVM

Benign

-0.68

PhyloP100

5.4

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.093

Sift

Pathogenic

0.0

.;D

Sift4G

Benign

0.32

T;T

Vest4

0.38

MPC

0.60

ClinPred

0.019

GERP RS

5.1

gMVP

0.31

Mutation Taster

=91/9

polymorphism

(source)

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

Publications

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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