Variant 6-158059300-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003898.4(SYNJ2):c.901G>A(p.Val301Met) variant causes a missense change. The variant allele was found at a frequency of 0.00034 in 1,550,836 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 (no stars).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

SYNJ2
NM_003898.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 5.38

Variant links:

Genes affected

SYNJ2 (HGNC:11504): (synaptojanin 2) The gene is a member of the inositol-polyphosphate 5-phosphatase family. The encoded protein interacts with the ras-related C3 botulinum toxin substrate 1, which causes translocation of the encoded protein to the plasma membrane where it inhibits clathrin-mediated endocytosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

SYNJ2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1989666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ2	NM_003898.4 linkuse as main transcript	c.901G>A	p.Val301Met	missense_variant	7/27	ENST00000355585.9	NP_003889.1	O15056-1B4DG94

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYNJ2	ENST00000355585.9 linkuse as main transcript	c.901G>A	p.Val301Met	missense_variant	7/27	1	NM_003898.4	ENSP00000347792.4	O15056-1
SYNJ2	ENST00000640338.1 linkuse as main transcript	c.901G>A	p.Val301Met	missense_variant	7/27	1		ENSP00000492532.1	O15056-3
SYNJ2	ENST00000638626.1 linkuse as main transcript	c.190G>A	p.Val64Met	missense_variant	6/26	1		ENSP00000492369.1	A0A1W2PR85
SYNJ2	ENST00000485863.1 linkuse as main transcript	n.379G>A		non_coding_transcript_exon_variant	4/6	3		ENSP00000436657.1	H0YEV8

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00220

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:

0.000544

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000218

AC:

AN:

155802

Hom.:

AF XY:

0.000183

AC XY:

AN XY:

81878

show subpopulations

Gnomad AFR exome

AF:

0.000114

Gnomad AMR exome

AF:

0.000162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000878

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000446

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000347

AC:

485

AN:

1398454

Hom.:

Cov.:

AF XY:

0.000305

AC XY:

210

AN XY:

689628

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

Gnomad4 AMR exome

AF:

0.000168

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000884

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000424

Gnomad4 OTH exome

AF:

0.000155

GnomAD4 genome

AF:

0.000276

AC:

AN:

152382

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0000721

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:

0.000544

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000416

Hom.:

Bravo

AF:

0.000283

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000494

AC:

ExAC

AF:

0.0000496

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Meniere disease

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Center for Computational Biology & Bioinformatics, University of California, San Diego

Jun 03, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.85

D;.;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Uncertain

0.25

MutationAssessor

Pathogenic

3.2

M;M;.

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.5

N;.;.

REVEL

Uncertain

0.54

Sift

Uncertain

0.0010

D;.;.

Sift4G

Uncertain

0.0030

D;.;.

Polyphen

0.99

D;D;.

Vest4

0.63

MVP

0.77

MPC

0.74

ClinPred

0.30

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.63

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