rs2833929

chr21-32641973-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_203446.3(SYNJ1):c.3518-7G>T variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008293

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.623

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 586760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32641973-C-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
SYNJ1	NM_203446.3 linkuse as main transcript	c.3518-7G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000674351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ1	ENST00000674351.1 linkuse as main transcript	c.3518-7G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_203446.3		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

GnomAD3 exomes

AF:

0.289

AC:

72536

AN:

250784

Hom.:

10847

AF XY:

0.294

AC XY:

39844

AN XY:

135608

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 SAS exome

AF:

0.321

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

Gnomad4 AFR exome

AF:

0.269

Gnomad4 AMR exome

AF:

0.274

Gnomad4 ASJ exome

AF:

0.405

Gnomad4 EAS exome

AF:

0.354

Gnomad4 SAS exome

AF:

0.321

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.278

Gnomad4 OTH exome

AF:

0.298

GnomAD4 genome

AF:

0.283

AC:

42932

AN:

151908

Hom.:

6113

Cov.:

AF XY:

0.283

AC XY:

20980

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.272

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.399

Gnomad4 EAS

AF:

0.345

Gnomad4 SAS

AF:

0.313

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.306

Alfa

AF:

0.291

Hom.:

3597

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:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Developmental and epileptic encephalopathy, 53

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Early-onset Parkinson disease 20

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

Cadd

Benign

5.6

Dann

Benign

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over