Variant rs2230766 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_203446.3(SYNJ1):c.3721C>T(p.Leu1241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0825 in 1,613,350 control chromosomes in the GnomAD database, including 6,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 476 hom., cov: 32)

Exomes 𝑓: 0.084 ( 5589 hom. )

Consequence

SYNJ1
NM_203446.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.07

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 21-32639102-G-A is Benign according to our data. Variant chr21-32639102-G-A is described in ClinVar as [Benign]. Clinvar id is 586761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-32639102-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ1	NM_203446.3 linkuse as main transcript	c.3721C>T	p.Leu1241=	synonymous_variant	31/33	ENST00000674351.1	NP_982271.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNJ1	ENST00000674351.1 linkuse as main transcript	c.3721C>T	p.Leu1241=	synonymous_variant	31/33		NM_203446.3	ENSP00000501530		O43426-2

Frequencies

GnomAD3 genomes

AF:

0.0675

AC:

10273

AN:

152136

Hom.:

476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.0861

Gnomad ASJ

AF:

0.0685

Gnomad EAS

AF:

0.00751

Gnomad SAS

AF:

0.0611

Gnomad FIN

AF:

0.0858

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0968

Gnomad OTH

AF:

0.0890

GnomAD3 exomes

AF:

0.0719

AC:

18071

AN:

251194

Hom.:

821

AF XY:

0.0741

AC XY:

10065

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.0126

Gnomad AMR exome

AF:

0.0459

Gnomad ASJ exome

AF:

0.0748

Gnomad EAS exome

AF:

0.00772

Gnomad SAS exome

AF:

0.0648

Gnomad FIN exome

AF:

0.0889

Gnomad NFE exome

AF:

0.0968

Gnomad OTH exome

AF:

0.0793

GnomAD4 exome

AF:

0.0841

AC:

122824

AN:

1461096

Hom.:

5589

Cov.:

AF XY:

0.0848

AC XY:

61627

AN XY:

726848

show subpopulations

Gnomad4 AFR exome

AF:

0.0131

Gnomad4 AMR exome

AF:

0.0483

Gnomad4 ASJ exome

AF:

0.0764

Gnomad4 EAS exome

AF:

0.00685

Gnomad4 SAS exome

AF:

0.0665

Gnomad4 FIN exome

AF:

0.0915

Gnomad4 NFE exome

AF:

0.0917

Gnomad4 OTH exome

AF:

0.0809

GnomAD4 genome

AF:

0.0675

AC:

10272

AN:

152254

Hom.:

476

Cov.:

AF XY:

0.0666

AC XY:

4958

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0147

Gnomad4 AMR

AF:

0.0860

Gnomad4 ASJ

AF:

0.0685

Gnomad4 EAS

AF:

0.00753

Gnomad4 SAS

AF:

0.0614

Gnomad4 FIN

AF:

0.0858

Gnomad4 NFE

AF:

0.0968

Gnomad4 OTH

AF:

0.0881

Alfa

AF:

0.0712

Hom.:

271

Bravo

AF:

0.0623

EpiCase

AF:

0.0965

EpiControl

AF:

0.0933

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.5

DANN

Benign

0.66

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