19-48955713-TGGGGGGG-TGGGGGG
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_138761.4(BAX):c.121delG(p.Glu41ArgfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,609,526 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
BAX
NM_138761.4 frameshift
NM_138761.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.473
Publications
17 publications found
Genes affected
BAX (HGNC:959): (BCL2 associated X, apoptosis regulator) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. The association and the ratio of BAX to BCL2 also determines survival or death of a cell following an apoptotic stimulus. This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and has been shown to be involved in P53-mediated apoptosis. Multiple alternatively spliced transcript variants, which encode different isoforms, have been reported for this gene. [provided by RefSeq, Dec 2019]
BAX Gene-Disease associations (from GenCC):
- leukemia, acute lymphocytic, susceptibility to, 1Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-48955713-TG-T is Pathogenic according to our data. Variant chr19-48955713-TG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 9512.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_138761.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BAX | NM_138761.4 | MANE Select | c.121delG | p.Glu41ArgfsTer19 | frameshift | Exon 3 of 6 | NP_620116.1 | ||
| BAX | NM_001291428.2 | c.121delG | p.Glu41ArgfsTer19 | frameshift | Exon 3 of 6 | NP_001278357.1 | |||
| BAX | NM_004324.4 | c.121delG | p.Glu41ArgfsTer19 | frameshift | Exon 3 of 5 | NP_004315.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BAX | ENST00000345358.12 | TSL:1 MANE Select | c.121delG | p.Glu41ArgfsTer19 | frameshift | Exon 3 of 6 | ENSP00000263262.9 | ||
| BAX | ENST00000293288.12 | TSL:1 | c.121delG | p.Glu41ArgfsTer19 | frameshift | Exon 3 of 5 | ENSP00000293288.8 | ||
| BAX | ENST00000415969.6 | TSL:1 | c.121delG | p.Glu41ArgfsTer19 | frameshift | Exon 3 of 6 | ENSP00000389971.2 |
Frequencies
GnomAD3 genomes 0.00000663 AC: 1AN: 150748Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
150748
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000625 AC: 15AN: 239912 AF XY: 0.0000692 show subpopulations
GnomAD2 exomes
AF:
AC:
15
AN:
239912
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1458778Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 17AN XY: 725524 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
32
AN:
1458778
Hom.:
Cov.:
30
AF XY:
AC XY:
17
AN XY:
725524
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33380
American (AMR)
AF:
AC:
3
AN:
44402
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
25962
East Asian (EAS)
AF:
AC:
2
AN:
39600
South Asian (SAS)
AF:
AC:
2
AN:
85984
European-Finnish (FIN)
AF:
AC:
0
AN:
53194
Middle Eastern (MID)
AF:
AC:
0
AN:
5742
European-Non Finnish (NFE)
AF:
AC:
22
AN:
1110278
Other (OTH)
AF:
AC:
2
AN:
60236
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000424234), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.341
Heterozygous variant carriers
0
3
7
10
14
17
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 0.00000663 AC: 1AN: 150748Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1AN XY: 73520 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
150748
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
73520
show subpopulations
African (AFR)
AF:
AC:
0
AN:
40958
American (AMR)
AF:
AC:
0
AN:
15142
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3458
East Asian (EAS)
AF:
AC:
0
AN:
5138
South Asian (SAS)
AF:
AC:
1
AN:
4722
European-Finnish (FIN)
AF:
AC:
0
AN:
10432
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67600
Other (OTH)
AF:
AC:
0
AN:
2072
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome 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
Alfa
AF:
Hom.:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Carcinoma of colon Pathogenic:1
Feb 14, 1997
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.