Variant 6-158017255-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003898.4(SYNJ2):c.179C>T(p.Ala60Val) variant causes a missense change. The variant allele was found at a frequency of 0.00225 in 1,613,908 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 14 hom. )

Consequence

SYNJ2
NM_003898.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.88

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01290378).

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ2	NM_003898.4 linkuse as main transcript	c.179C>T	p.Ala60Val	missense_variant	2/27	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.179C>T	p.Ala60Val	missense_variant	2/27	1	NM_003898.4	ENSP00000347792.4	O15056-1
SYNJ2	ENST00000640338.1 linkuse as main transcript	c.179C>T	p.Ala60Val	missense_variant	2/27	1		ENSP00000492532.1	O15056-3
SYNJ2	ENST00000638626 linkuse as main transcript	c.-533C>T		5_prime_UTR_variant	1/26	1		ENSP00000492369.1	A0A1W2PR85
SYNJ2	ENST00000367113.5 linkuse as main transcript	c.101C>T	p.Ala34Val	missense_variant	2/4	2		ENSP00000356080.4	H7BY56

Frequencies

GnomAD3 genomes

AF:

0.00244

AC:

371

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00782

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00332

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00228

AC:

572

AN:

251190

Hom.:

AF XY:

0.00248

AC XY:

337

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.00533

Gnomad NFE exome

AF:

0.00334

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00224

AC:

3267

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

1739

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00165

Gnomad4 FIN exome

AF:

0.00474

Gnomad4 NFE exome

AF:

0.00241

Gnomad4 OTH exome

AF:

0.00235

GnomAD4 genome

AF:

0.00244

AC:

371

AN:

152210

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

184

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000506

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00782

Gnomad4 NFE

AF:

0.00332

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00297

Hom.:

Bravo

AF:

0.00184

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00242

AC:

294

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00327

EpiControl

AF:

0.00255

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

Benign

0.34

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.63

D;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.55

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.068

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.4

D;.

REVEL

Uncertain

0.42

Sift

Benign

0.15

T;.

Sift4G

Uncertain

0.047

D;.

Polyphen

1.0

D;D

Vest4

0.86

MVP

0.53

MPC

0.23

ClinPred

0.024

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.46

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