NM_203446.3:c.2346G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1

The NM_203446.3(SYNJ1):c.2346G>A(p.Pro782Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,613,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

SYNJ1
NM_203446.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.32

Publications

1 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 21-32657831-C-T is Benign according to our data. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32657831-C-T is described in CliVar as Likely_benign. Clinvar id is 478333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.33 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000828 (126/152256) while in subpopulation NFE AF = 0.00148 (101/68020). AF 95% confidence interval is 0.00125. There are 0 homozygotes in GnomAd4. There are 55 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ1	NM_203446.3 link	c.2346G>A	p.Pro782Pro	synonymous_variant	Exon 19 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.2346G>A	p.Pro782Pro	synonymous_variant	Exon 19 of 33		NM_203446.3	ENSP00000501530.1		O43426-2

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000792

AC:

199

AN:

251118

AF XY:

0.000840

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00144

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.00116

AC:

1694

AN:

1461574

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

814

AN XY:

727098

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33456

American (AMR)

AF:

0.000202

AC:

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.00107

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00142

AC:

1574

AN:

1111882

Other (OTH)

AF:

0.000828

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

160

241

321

401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

168

224

280

<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:

0.000828

AC:

126

AN:

152256

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41540

American (AMR)

AF:

0.0000654

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000660

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00148

AC:

101

AN:

68020

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000975

Hom.:

Bravo

AF:

0.000703

EpiCase

AF:

0.00120

EpiControl

AF:

0.00101

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SYNJ1: BP4, BP7 -

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 29, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

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:Likely 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

-0.46

CADD

Benign

2.1

(source)

DANN

Benign

0.72

PhyloP100

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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