Variant rs147931121 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_203446.3(SYNJ1):c.3139C>G(p.Arg1047Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000151 in 1,614,008 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 Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

SYNJ1
NM_203446.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 5.54

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31846622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ1	NM_203446.3 linkuse as main transcript	c.3139C>G	p.Arg1047Gly	missense_variant	24/33	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.3139C>G	p.Arg1047Gly	missense_variant	24/33		NM_203446.3	ENSP00000501530.1		O43426-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251496

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000156

AC:

228

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

124

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

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:

0.000198

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000105

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000169

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2021

The c.3256C>G (p.R1086G) alteration is located in exon 24 (coding exon 24) of the SYNJ1 gene. This alteration results from a C to G substitution at nucleotide position 3256, causing the arginine (R) at amino acid position 1086 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

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

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 30, 2022

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1086 of the SYNJ1 protein (p.Arg1086Gly). This variant is present in population databases (rs147931121, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SYNJ1-related conditions. ClinVar contains an entry for this variant (Variation ID: 576516). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.00031

BayesDel_noAF

Uncertain

0.070

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

.;T;.;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.020

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

D;D;D;D;D

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.32

T;T;T;T;T

MetaSVM

Uncertain

0.51

MutationAssessor

Uncertain

2.0

M;.;.;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.0

N;N;.;N;N

REVEL

Uncertain

0.55

Sift

Benign

0.26

T;T;.;T;T

Sift4G

Benign

0.37

T;T;T;T;T

Polyphen

0.0030

B;.;.;B;.

Vest4

0.69

MVP

0.80

MPC

0.19

ClinPred

0.54

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.28

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