rs2833929

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_203446.3(SYNJ1):c.3518-7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,613,026 control chromosomes in the GnomAD database, including 65,816 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6113 hom., cov: 31)

Exomes 𝑓: 0.28 ( 59703 hom. )

Consequence

SYNJ1
NM_203446.3 splice_region, intron

Scores

Splicing: ADA: 0.00008293

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.623

Publications

14 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 (BayesDel_noAF=-0.65).

BP6

Variant 21-32641973-C-A is Benign according to our data. Variant chr21-32641973-C-A is described in ClinVar as Benign. ClinVar VariationId is 586760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ1	NM_203446.3 link	c.3518-7G>T		splice_region_variant, intron_variant	Intron 28 of 32	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.3518-7G>T		splice_region_variant, intron_variant	Intron 28 of 32		NM_203446.3	ENSP00000501530.1		O43426-2

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42907

AN:

151788

Hom.:

6106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.272

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.345

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.375

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.305

GnomAD2 exomes

AF:

0.289

AC:

72536

AN:

250784

AF XY:

0.294

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.268

Gnomad ASJ exome

AF:

0.403

Gnomad EAS exome

AF:

0.337

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.283

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.284

AC:

414806

AN:

1461118

Hom.:

59703

Cov.:

AF XY:

0.286

AC XY:

207711

AN XY:

726904

show subpopulations

African (AFR)

AF:

0.269

AC:

8997

AN:

33428

American (AMR)

AF:

0.274

AC:

12262

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

10573

AN:

26126

East Asian (EAS)

AF:

0.354

AC:

14058

AN:

39674

South Asian (SAS)

AF:

0.321

AC:

27642

AN:

86210

European-Finnish (FIN)

AF:

0.233

AC:

12431

AN:

53386

Middle Eastern (MID)

AF:

0.345

AC:

1989

AN:

5764

European-Non Finnish (NFE)

AF:

0.278

AC:

308886

AN:

1111486

Other (OTH)

AF:

0.298

AC:

17968

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

14683

29366

44048

58731

73414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10416

20832

31248

41664

52080

<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:

0.283

AC:

42932

AN:

151908

Hom.:

6113

Cov.:

AF XY:

0.283

AC XY:

20980

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.272

AC:

11254

AN:

41408

American (AMR)

AF:

0.278

AC:

4244

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1382

AN:

3468

East Asian (EAS)

AF:

0.345

AC:

1779

AN:

5150

South Asian (SAS)

AF:

0.313

AC:

1511

AN:

4820

European-Finnish (FIN)

AF:

0.227

AC:

2394

AN:

10530

Middle Eastern (MID)

AF:

0.359

AC:

104

AN:

290

European-Non Finnish (NFE)

AF:

0.285

AC:

19395

AN:

67958

Other (OTH)

AF:

0.306

AC:

646

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1555

3110

4666

6221

7776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.290

Hom.:

3619

Bravo

AF:

0.287

Asia WGS

AF:

0.299

AC:

1041

AN:

3478

EpiCase

AF:

0.300

EpiControl

AF:

0.300

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 05, 2018

GeneDx

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

- -

not specified

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

Developmental and epileptic encephalopathy, 53

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Early-onset Parkinson disease 20

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.6

(source)

DANN

Benign

0.68

PhyloP100

-0.62

PromoterAI

0.0034

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000083

dbscSNV1_RF

Benign

0.0

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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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