rs61755328

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_203446.3(SYNJ1):c.43C>T(p.Pro15Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000755 in 1,614,100 control chromosomes in the GnomAD database, including 8 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 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 3 hom. )

Consequence

SYNJ1
NM_203446.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 9.43

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010415465).

BP6

Variant 21-32726853-G-A is Benign according to our data. Variant chr21-32726853-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00411 (626/152224) while in subpopulation AFR AF = 0.0144 (597/41528). AF 95% confidence interval is 0.0134. There are 5 homozygotes in GnomAd4. There are 316 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ1	NM_203446.3 link	c.43C>T	p.Pro15Ser	missense_variant	Exon 2 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.43C>T	p.Pro15Ser	missense_variant	Exon 2 of 33		NM_203446.3	ENSP00000501530.1		O43426-2

Frequencies

GnomAD3 genomes

AF:

0.00410

AC:

623

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00114

AC:

286

AN:

251486

AF XY:

0.000809

show subpopulations

Gnomad AFR exome

AF:

0.0162

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000405

AC:

592

AN:

1461876

Hom.:

Cov.:

AF XY:

0.000367

AC XY:

267

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0146

AC:

490

AN:

33480

American (AMR)

AF:

0.000514

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1112010

Other (OTH)

AF:

0.00108

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

103

137

171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00411

AC:

626

AN:

152224

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

316

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0144

AC:

597

AN:

41528

American (AMR)

AF:

0.00111

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68012

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

107

142

178

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:

0.00231

Hom.:

Bravo

AF:

0.00488

ESP6500AA

AF:

0.0143

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00138

AC:

168

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Jun 01, 2018

Athena Diagnostics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 11, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 12, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

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: BS1 -

Sep 06, 2021

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

Jan 30, 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

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

.;T;.;T;T;.;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.97

D;D;D;D;D;D;D

MetaRNN

Benign

0.010

T;T;T;T;T;T;T

MetaSVM

Uncertain

0.74

MutationAssessor

Benign

1.9

L;.;.;.;.;.;.

PhyloP100

9.4

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.9

D;D;.;D;D;D;D

REVEL

Pathogenic

0.70

Sift

Benign

0.10

T;T;.;T;T;T;D

Sift4G

Benign

0.23

T;T;T;T;T;.;.

Polyphen

0.99

D;.;.;P;.;.;.

Vest4

0.63

MVP

0.89

MPC

1.5

ClinPred

0.029

GERP RS

4.5

PromoterAI

-0.038

Neutral

(source)

gMVP

0.57

Mutation Taster

=91/9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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