dbSNP rs2502601: SYNJ2:p.Glu1468Gly (chr6-158096276-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003898.4(SYNJ2):c.4403A>G(p.Glu1468Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,613,888 control chromosomes in the GnomAD database, including 213,305 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.53 ( 21292 hom., cov: 33)

Exomes 𝑓: 0.51 ( 192013 hom. )

Consequence

SYNJ2
NM_003898.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0420

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2998245E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ2	NM_003898.4 link	c.4403A>G	p.Glu1468Gly	missense_variant	Exon 27 of 27	ENST00000355585.9	NP_003889.1	O15056-1B4DG94

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYNJ2	ENST00000355585.9 link	c.4403A>G	p.Glu1468Gly	missense_variant	Exon 27 of 27	1	NM_003898.4	ENSP00000347792.4	O15056-1
SYNJ2	ENST00000638626.1 link	c.3692A>G	p.Glu1231Gly	missense_variant	Exon 26 of 26	1		ENSP00000492369.1	A0A1W2PR85
SYNJ2	ENST00000367122.6 link	c.2432A>G	p.Glu811Gly	missense_variant	Exon 14 of 14	1		ENSP00000356089.3	E7ER60
SYNJ2	ENST00000367112.1 link	n.3513A>G		non_coding_transcript_exon_variant	Exon 10 of 10	2

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79864

AN:

152012

Hom.:

21275

Cov.:

show subpopulations

Gnomad AFR

AF:

0.591

Gnomad AMI

AF:

0.703

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.565

Gnomad SAS

AF:

0.572

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.417

Gnomad NFE

AF:

0.509

Gnomad OTH

AF:

0.518

GnomAD3 exomes

AF:

0.503

AC:

126092

AN:

250752

Hom.:

32756

AF XY:

0.507

AC XY:

68853

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.595

Gnomad AMR exome

AF:

0.323

Gnomad ASJ exome

AF:

0.467

Gnomad EAS exome

AF:

0.575

Gnomad SAS exome

AF:

0.558

Gnomad FIN exome

AF:

0.544

Gnomad NFE exome

AF:

0.514

Gnomad OTH exome

AF:

0.492

GnomAD4 exome

AF:

0.510

AC:

745060

AN:

1461758

Hom.:

192013

Cov.:

AF XY:

0.511

AC XY:

371291

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.599

Gnomad4 AMR exome

AF:

0.327

Gnomad4 ASJ exome

AF:

0.465

Gnomad4 EAS exome

AF:

0.508

Gnomad4 SAS exome

AF:

0.551

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.510

Gnomad4 OTH exome

AF:

0.523

GnomAD4 genome

AF:

0.525

AC:

79913

AN:

152130

Hom.:

21292

Cov.:

AF XY:

0.525

AC XY:

39056

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.591

Gnomad4 AMR

AF:

0.384

Gnomad4 ASJ

AF:

0.474

Gnomad4 EAS

AF:

0.565

Gnomad4 SAS

AF:

0.570

Gnomad4 FIN

AF:

0.545

Gnomad4 NFE

AF:

0.509

Gnomad4 OTH

AF:

0.516

Alfa

AF:

0.505

Hom.:

49071

Bravo

AF:

0.516

TwinsUK

AF:

0.515

AC:

1909

ALSPAC

AF:

0.513

AC:

1979

ESP6500AA

AF:

0.582

AC:

2563

ESP6500EA

AF:

0.509

AC:

4379

ExAC

AF:

0.513

AC:

62317

Asia WGS

AF:

0.571

AC:

1988

AN:

3478

EpiCase

AF:

0.501

EpiControl

AF:

0.498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.71

DANN

Benign

0.88

DEOGEN2

Benign

0.23

T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.56

T;T;T

MetaRNN

Benign

0.000013

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

-0.69

N;.;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.010

N;.;.

REVEL

Benign

0.15

Sift

Benign

0.82

T;.;.

Sift4G

Benign

0.39

T;.;T

Polyphen

0.0

B;.;.

Vest4

0.033

MPC

0.22

ClinPred

0.0046

GERP RS

0.080

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.061

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over