chr19-48955713-TG-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 9P and 4B. PVS1PP5BS2
The NM_138761.4(BAX):c.121del(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
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
Variant 19-48955713-TG-T is Pathogenic according to our data. Variant chr19-48955713-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 9512.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAdExome4 at 32 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BAX | NM_138761.4 | c.121del | p.Glu41ArgfsTer19 | frameshift_variant | 3/6 | ENST00000345358.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BAX | ENST00000345358.12 | c.121del | p.Glu41ArgfsTer19 | frameshift_variant | 3/6 | 1 | NM_138761.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000663 AC: 1AN: 150748Hom.: 0 Cov.: 31
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:
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1458778Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 17AN XY: 725524
GnomAD4 exome
AF:
AC:
32
AN:
1458778
Hom.:
Cov.:
30
AF XY:
AC XY:
17
AN XY:
725524
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00000663 AC: 1AN: 150748Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1AN XY: 73520
GnomAD4 genome
AF:
AC:
1
AN:
150748
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
73520
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Carcinoma of colon Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 14, 1997 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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