rs2254562

Variant names:

Variant summary

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

The NM_203446.3(SYNJ1):c.884A>G(p.Lys295Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,530,650 control chromosomes in the GnomAD database, including 61,131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.29 ( 6568 hom., cov: 32)

Exomes 𝑓: 0.28 ( 54563 hom. )

Consequence

SYNJ1
NM_203446.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 7.68

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 (MetaRNN=0.0017498434).

BP6

Variant 21-32687042-T-C is Benign according to our data. Variant chr21-32687042-T-C is described in ClinVar as [Benign]. Clinvar id is 586758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32687042-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ1	NM_203446.3 link	c.884A>G	p.Lys295Arg	missense_variant	Exon 8 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.884A>G	p.Lys295Arg	missense_variant	Exon 8 of 33		NM_203446.3	ENSP00000501530.1		O43426-2

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44433

AN:

151940

Hom.:

6560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.315

GnomAD3 exomes

AF:

0.276

AC:

54049

AN:

195550

Hom.:

7831

AF XY:

0.281

AC XY:

30141

AN XY:

107448

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.238

Gnomad ASJ exome

AF:

0.392

Gnomad EAS exome

AF:

0.307

Gnomad SAS exome

AF:

0.306

Gnomad FIN exome

AF:

0.223

Gnomad NFE exome

AF:

0.273

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.278

AC:

383206

AN:

1378592

Hom.:

54563

Cov.:

AF XY:

0.280

AC XY:

192049

AN XY:

686456

show subpopulations

Gnomad4 AFR exome

AF:

0.293

Gnomad4 AMR exome

AF:

0.254

Gnomad4 ASJ exome

AF:

0.399

Gnomad4 EAS exome

AF:

0.346

Gnomad4 SAS exome

AF:

0.311

Gnomad4 FIN exome

AF:

0.232

Gnomad4 NFE exome

AF:

0.272

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.292

AC:

44460

AN:

152058

Hom.:

6568

Cov.:

AF XY:

0.292

AC XY:

21671

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.305

Gnomad4 AMR

AF:

0.281

Gnomad4 ASJ

AF:

0.398

Gnomad4 EAS

AF:

0.347

Gnomad4 SAS

AF:

0.314

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.286

Gnomad4 OTH

AF:

0.316

Alfa

AF:

0.297

Hom.:

12796

Bravo

AF:

0.298

TwinsUK

AF:

0.285

AC:

1055

ALSPAC

AF:

0.281

AC:

1083

ESP6500AA

AF:

0.297

AC:

1307

ESP6500EA

AF:

0.298

AC:

2559

ExAC

AF:

0.292

AC:

35398

Asia WGS

AF:

0.303

AC:

1054

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

.;T;.;T;T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.69

T;T;T;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.;.;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.6

N;N;.;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.040

D;T;.;D;T;T

Sift4G

Benign

0.20

T;T;T;T;T;.

Polyphen

0.99

D;.;.;B;.;.

Vest4

0.37

MPC

1.3

ClinPred

0.021

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.26

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

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