rs61756694

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_203446.3(SYNJ1):c.573A>G(p.Thr191Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00603 in 1,614,172 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 37 hom. )

Consequence

SYNJ1
NM_203446.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.220

Publications

4 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 21-32695189-T-C is Benign according to our data. Variant chr21-32695189-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 478365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.22 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00408 (621/152336) while in subpopulation NFE AF = 0.00631 (429/68032). AF 95% confidence interval is 0.00581. There are 3 homozygotes in GnomAd4. There are 292 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ1	NM_203446.3 link	c.573A>G	p.Thr191Thr	synonymous_variant	Exon 5 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.573A>G	p.Thr191Thr	synonymous_variant	Exon 5 of 33		NM_203446.3	ENSP00000501530.1		O43426-2

Frequencies

GnomAD3 genomes

AF:

0.00409

AC:

623

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00632

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00485

AC:

1220

AN:

251470

AF XY:

0.00531

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00416

Gnomad NFE exome

AF:

0.00743

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00623

AC:

9108

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00632

AC XY:

4599

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.00134

AC:

AN:

33478

American (AMR)

AF:

0.00195

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00157

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00555

AC:

479

AN:

86258

European-Finnish (FIN)

AF:

0.00358

AC:

191

AN:

53420

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00714

AC:

7938

AN:

1111984

Other (OTH)

AF:

0.00513

AC:

310

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

510

1020

1529

2039

2549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.00408

AC:

621

AN:

152336

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

292

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00115

AC:

AN:

41574

American (AMR)

AF:

0.00464

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00476

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00358

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00631

AC:

429

AN:

68032

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

126

157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00492

Hom.:

Bravo

AF:

0.00412

Asia WGS

AF:

0.00173

AC:

AN:

3476

EpiCase

AF:

0.00496

EpiControl

AF:

0.00581

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Apr 10, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SYNJ1: BP4, BP7, BS2 -

Nov 09, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

SYNJ1-related disorder

Benign:1

Dec 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.8

(source)

DANN

Benign

0.38

PhyloP100

-0.22

Mutation Taster

=99/1

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