Variant rs76056543 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000433931.7(SYNJ1):c.4640C>T(p.Pro1547Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,614,146 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00058 ( 7 hom. )

Consequence

SYNJ1
ENST00000433931.7 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.16

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=0.0035976171).

BP6

Variant 21-32631194-G-A is Benign according to our data. Variant chr21-32631194-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 478360.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 = 0.00558 (849/152274) while in subpopulation AFR AF= 0.0195 (810/41556). AF 95% confidence interval is 0.0184. There are 8 homozygotes in gnomad4. There are 391 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ1	NM_203446.3 linkuse as main transcript	c.*611C>T		3_prime_UTR_variant	33/33	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.*611C>T		3_prime_UTR_variant	33/33		NM_203446.3	ENSP00000501530		O43426-2

Frequencies

GnomAD3 genomes

AF:

0.00556

AC:

846

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

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:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00158

AC:

398

AN:

251462

Hom.:

AF XY:

0.00124

AC XY:

168

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0228

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000575

AC:

841

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000465

AC XY:

338

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0216

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.00558

AC:

849

AN:

152274

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

391

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0195

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00645

ESP6500AA

AF:

0.0195

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00180

AC:

218

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 17, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 14, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.2

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

.;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0036

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.029

Sift

Uncertain

0.0030

.;D

Sift4G

Benign

0.26

T;T

Vest4

0.076

MVP

0.44

MPC

0.12

ClinPred

0.016

GERP RS

3.7

gMVP

0.17

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