rs61755328

Positions:

Variant summary

Our verdict is Benign. Variant got -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:5

Conservation

PhyloP100: 9.43

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=0.010415465).

BP6

Variant 21-32726853-G-A is Benign according to our data. Variant chr21-32726853-G-A is described in ClinVar as [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ1	NM_203446.3 linkuse as main transcript	c.43C>T	p.Pro15Ser	missense_variant	2/33	ENST00000674351.1	NP_982271.3	O43426-2C9JFZ1Q05CZ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNJ1	ENST00000674351.1 linkuse as main transcript	c.43C>T	p.Pro15Ser	missense_variant	2/33		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

GnomAD3 exomes

AF:

0.00114

AC:

286

AN:

251486

Hom.:

AF XY:

0.000809

AC XY:

110

AN XY:

135914

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 SAS exome

AF:

0.0000327

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

Gnomad4 AFR exome

AF:

0.0146

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.00411

AC:

626

AN:

152224

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

316

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0144

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00191

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 01, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 12, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	SYNJ1: BS1 -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

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;.;.;.;.;.;.

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

gMVP

0.57

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