Genetic Variant ENST00000640338.1:c.*69C>T (chr6-158094079-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 ENST00000640338.1(SYNJ2):c.*69C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 723,194 control chromosomes in the GnomAD database, including 19,893 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 0.18 ( 3128 hom., cov: 31)

Exomes 𝑓: 0.23 ( 16765 hom. )

Consequence

SYNJ2
ENST00000640338.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.468

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000640338.1. 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.3744+975C>T	intron	N/A	NP_003889.1	O15056-1
SYNJ2	NM_001410947.1		c.*27+42C>T	intron	N/A	NP_001397876.1	O15056-3
SYNJ2	NM_001178088.2		c.3033+975C>T	intron	N/A	NP_001171559.1	A0A1W2PR85

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYNJ2	ENST00000640338.1	TSL:1	c.*69C>T	3_prime_UTR	Exon 27 of 27	ENSP00000492532.1	O15056-3
SYNJ2	ENST00000355585.9	TSL:1 MANE Select	c.3744+975C>T	intron	N/A	ENSP00000347792.4	O15056-1
SYNJ2	ENST00000638626.1	TSL:1	c.3033+975C>T	intron	N/A	ENSP00000492369.1	A0A1W2PR85

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28055

AN:

151928

Hom.:

3131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0682

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.0129

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.221

GnomAD4 exome

AF:

0.229

AC:

130954

AN:

571148

Hom.:

16765

Cov.:

AF XY:

0.235

AC XY:

72584

AN XY:

309212

show subpopulations

African (AFR)

AF:

0.0701

AC:

1146

AN:

16346

American (AMR)

AF:

0.150

AC:

5842

AN:

39058

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

6809

AN:

19470

East Asian (EAS)

AF:

0.00636

AC:

222

AN:

34926

South Asian (SAS)

AF:

0.236

AC:

15043

AN:

63648

European-Finnish (FIN)

AF:

0.172

AC:

6339

AN:

36776

Middle Eastern (MID)

AF:

0.382

AC:

1374

AN:

3594

European-Non Finnish (NFE)

AF:

0.266

AC:

86934

AN:

326234

Other (OTH)

AF:

0.233

AC:

7245

AN:

31096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

4827

9655

14482

19310

24137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.184

AC:

28051

AN:

152046

Hom.:

3128

Cov.:

AF XY:

0.181

AC XY:

13461

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0683

AC:

2833

AN:

41486

American (AMR)

AF:

0.186

AC:

2847

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

1207

AN:

3472

East Asian (EAS)

AF:

0.0130

AC:

AN:

5170

South Asian (SAS)

AF:

0.215

AC:

1034

AN:

4804

European-Finnish (FIN)

AF:

0.170

AC:

1798

AN:

10578

Middle Eastern (MID)

AF:

0.377

AC:

110

AN:

292

European-Non Finnish (NFE)

AF:

0.257

AC:

17450

AN:

67958

Other (OTH)

AF:

0.219

AC:

460

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1096

2192

3288

4384

5480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.225

Hom.:

2183

Bravo

AF:

0.181

Asia WGS

AF:

0.107

AC:

372

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.2

(source)

DANN

Benign

0.64

PhyloP100

-0.47

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