Genetic Variant SYNJ2:c.128-16156C>T (chr6-158001048-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003898.4(SYNJ2):c.128-16156C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,782 control chromosomes in the GnomAD database, including 1,113 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 0.11 ( 1110 hom., cov: 31)

Exomes 𝑓: 0.11 ( 3 hom. )

Consequence

SYNJ2
NM_003898.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

7 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:

SYNJ2-IT1 (HGNC:41387): (SYNJ2 intronic transcript 1)

SYNJ2-IT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003898.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYNJ2	NM_003898.4	MANE Select	c.128-16156C>T	intron	N/A	NP_003889.1	O15056-1
SYNJ2	NM_001410947.1		c.128-16156C>T	intron	N/A	NP_001397876.1	O15056-3
SYNJ2-IT1	NR_046796.1		n.-59C>T	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYNJ2	ENST00000355585.9	TSL:1 MANE Select	c.128-16156C>T	intron	N/A	ENSP00000347792.4	O15056-1
SYNJ2	ENST00000640338.1	TSL:1	c.128-16156C>T	intron	N/A	ENSP00000492532.1	O15056-3
SYNJ2	ENST00000367113.5	TSL:2	c.50-16156C>T	intron	N/A	ENSP00000356080.4	H7BY56

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16268

AN:

152042

Hom.:

1114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0377

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.0916

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.111

GnomAD4 exome

AF:

0.106

AC:

AN:

624

Hom.:

AF XY:

0.0995

AC XY:

AN XY:

382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.125

AC:

AN:

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

0.0992

AC:

AN:

242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.121

AC:

AN:

306

Other (OTH)

AF:

0.0500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.107

AC:

16254

AN:

152158

Hom.:

1110

Cov.:

AF XY:

0.107

AC XY:

7995

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0376

AC:

1560

AN:

41514

American (AMR)

AF:

0.110

AC:

1687

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

607

AN:

3472

East Asian (EAS)

AF:

0.153

AC:

792

AN:

5172

South Asian (SAS)

AF:

0.242

AC:

1165

AN:

4818

European-Finnish (FIN)

AF:

0.0916

AC:

970

AN:

10592

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9131

AN:

67986

Other (OTH)

AF:

0.112

AC:

236

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

737

1474

2212

2949

3686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.129

Hom.:

2442

Bravo

AF:

0.103

Asia WGS

AF:

0.195

AC:

680

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.53

(source)

DANN

Benign

0.56

PhyloP100

-1.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over