dbSNP rs1744173: SYNJ2:p.Gly1030Gly (chr6-158084056-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003898.4(SYNJ2):c.3090A>G(p.Gly1030Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 1,613,910 control chromosomes in the GnomAD database, including 575,076 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.85 ( 56002 hom., cov: 31)

Exomes 𝑓: 0.84 ( 519074 hom. )

Consequence

SYNJ2
NM_003898.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.148

Publications

22 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP7

Synonymous conserved (PhyloP=0.148 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ2	NM_003898.4 link	c.3090A>G	p.Gly1030Gly	synonymous_variant	Exon 22 of 27	ENST00000355585.9	NP_003889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNJ2	ENST00000355585.9 link	c.3090A>G	p.Gly1030Gly	synonymous_variant	Exon 22 of 27	1	NM_003898.4	ENSP00000347792.4

Frequencies

GnomAD3 genomes

AF:

0.851

AC:

129348

AN:

151972

Hom.:

55957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.962

Gnomad AMI

AF:

0.957

Gnomad AMR

AF:

0.648

Gnomad ASJ

AF:

0.907

Gnomad EAS

AF:

0.587

Gnomad SAS

AF:

0.812

Gnomad FIN

AF:

0.776

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.859

Gnomad OTH

AF:

0.848

GnomAD2 exomes

AF:

0.788

AC:

198244

AN:

251474

AF XY:

0.800

show subpopulations

Gnomad AFR exome

AF:

0.965

Gnomad AMR exome

AF:

0.501

Gnomad ASJ exome

AF:

0.904

Gnomad EAS exome

AF:

0.595

Gnomad FIN exome

AF:

0.774

Gnomad NFE exome

AF:

0.864

Gnomad OTH exome

AF:

0.813

GnomAD4 exome

AF:

0.838

AC:

1224956

AN:

1461820

Hom.:

519074

Cov.:

AF XY:

0.838

AC XY:

609723

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.970

AC:

32467

AN:

33480

American (AMR)

AF:

0.515

AC:

23040

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.901

AC:

23556

AN:

26136

East Asian (EAS)

AF:

0.531

AC:

21061

AN:

39696

South Asian (SAS)

AF:

0.818

AC:

70580

AN:

86258

European-Finnish (FIN)

AF:

0.774

AC:

41355

AN:

53418

Middle Eastern (MID)

AF:

0.913

AC:

5265

AN:

5768

European-Non Finnish (NFE)

AF:

0.860

AC:

956505

AN:

1111944

Other (OTH)

AF:

0.847

AC:

51127

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

10956

21912

32867

43823

54779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21100

42200

63300

84400

105500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.851

AC:

129434

AN:

152090

Hom.:

56002

Cov.:

AF XY:

0.843

AC XY:

62664

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.962

AC:

39931

AN:

41516

American (AMR)

AF:

0.647

AC:

9875

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.907

AC:

3148

AN:

3472

East Asian (EAS)

AF:

0.587

AC:

3029

AN:

5156

South Asian (SAS)

AF:

0.813

AC:

3909

AN:

4810

European-Finnish (FIN)

AF:

0.776

AC:

8204

AN:

10570

Middle Eastern (MID)

AF:

0.898

AC:

264

AN:

294

European-Non Finnish (NFE)

AF:

0.859

AC:

58421

AN:

67982

Other (OTH)

AF:

0.844

AC:

1780

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

888

1776

2663

3551

4439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.865

Hom.:

108409

Bravo

AF:

0.844

Asia WGS

AF:

0.717

AC:

2495

AN:

3478

EpiCase

AF:

0.870

EpiControl

AF:

0.873

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.3

(source)

DANN

Benign

0.27

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over