ENST00000433931.7:c.4830A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7

The ENST00000433931.7(SYNJ1):​c.4830A>G​(p.Thr1610Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,458,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SYNJ1
ENST00000433931.7 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.301

Publications

0 publications found
Variant links:
Genes affected
SYNJ1 (HGNC:11503): (synaptojanin 1) This gene encodes a phosphoinositide phosphatase that regulates levels of membrane phosphatidylinositol-4,5-bisphosphate. As such, expression of this enzyme may affect synaptic transmission and membrane trafficking. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
SYNJ1 Gene-Disease associations (from GenCC):
  • genetic developmental and epileptic encephalopathy
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • developmental and epileptic encephalopathy, 53
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • early-onset Parkinson disease 20
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
  • undetermined early-onset epileptic encephalopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • atypical juvenile parkinsonism
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • young-onset Parkinson disease
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4
Computational evidence support a benign effect (REVEL=0.04).
BP6
Variant 21-32631004-T-C is Benign according to our data. Variant chr21-32631004-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2156232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.301 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNJ1NM_203446.3 linkc.*801A>G 3_prime_UTR_variant Exon 33 of 33 ENST00000674351.1 NP_982271.3 O43426-2C9JFZ1Q05CZ1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNJ1ENST00000674351.1 linkc.*801A>G 3_prime_UTR_variant Exon 33 of 33 NM_203446.3 ENSP00000501530.1 O43426-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.0000282
AC:
7
AN:
248472
AF XY:
0.0000298
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000718
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1458446
Hom.:
0
Cov.:
30
AF XY:
0.0000138
AC XY:
10
AN XY:
725260
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33292
American (AMR)
AF:
0.00
AC:
0
AN:
44160
Ashkenazi Jewish (ASJ)
AF:
0.000425
AC:
11
AN:
25896
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39624
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86088
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53338
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5730
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1110136
Other (OTH)
AF:
0.0000498
AC:
3
AN:
60182
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
2
4
5
7
9
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
33
Alfa
AF:
0.000102
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Early-onset Parkinson disease 20;C4479313:Developmental and epileptic encephalopathy, 53 Benign:1
Feb 03, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
Jun 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

SYNJ1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
3.6
DANN
Benign
0.40
PhyloP100
0.30

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

Other links and lift over

dbSNP: rs747065956; hg19: chr21-34003314; API