Variant 6-158062145-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003898.4(SYNJ2):c.1108G>T(p.Gly370Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000372 in 1,613,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

SYNJ2
NM_003898.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.64

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ2	NM_003898.4 linkuse as main transcript	c.1108G>T	p.Gly370Trp	missense_variant	8/27	ENST00000355585.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ2	ENST00000355585.9 linkuse as main transcript	c.1108G>T	p.Gly370Trp	missense_variant	8/27	1	NM_003898.4	P2	O15056-1
SYNJ2	ENST00000640338.1 linkuse as main transcript	c.1108G>T	p.Gly370Trp	missense_variant	8/27	1		A2	O15056-3
SYNJ2	ENST00000638626.1 linkuse as main transcript	c.397G>T	p.Gly133Trp	missense_variant	7/26	1
SYNJ2	ENST00000485863.1 linkuse as main transcript	c.*212G>T		3_prime_UTR_variant, NMD_transcript_variant	5/6	3

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251268

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.0000289

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461500

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000164

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.000555

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.000166

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.1108G>T (p.G370W) alteration is located in exon 8 (coding exon 8) of the SYNJ2 gene. This alteration results from a G to T substitution at nucleotide position 1108, causing the glycine (G) at amino acid position 370 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.49

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Pathogenic

0.84

D;.;.

Eigen

Pathogenic

0.76

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Pathogenic

0.35

MetaRNN

Pathogenic

0.81

D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.8

H;H;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-4.2

D;.;.

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0020

D;.;.

Sift4G

Uncertain

0.012

D;.;.

Polyphen

1.0

D;D;.

Vest4

0.71

MVP

0.93

MPC

0.72

ClinPred

0.94

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.59

gMVP

0.53

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