rs1060500101
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_002382.5(MAX):c.211_221del(p.Ile71AlafsTer12) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. I71I) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
MAX
NM_002382.5 frameshift
NM_002382.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.27
Genes affected
MAX (HGNC:6913): (MYC associated factor X) The protein encoded by this gene is a member of the basic helix-loop-helix leucine zipper (bHLHZ) family of transcription factors. It is able to form homodimers and heterodimers with other family members, which include Mad, Mxi1 and Myc. Myc is an oncoprotein implicated in cell proliferation, differentiation and apoptosis. The homodimers and heterodimers compete for a common DNA target site (the E box) and rearrangement among these dimer forms provides a complex system of transcriptional regulation. Mutations of this gene have been reported to be associated with hereditary pheochromocytoma. A pseudogene of this gene is located on the long arm of chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 21 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 14-65077986-CATATACTGGAT-C is Pathogenic according to our data. Variant chr14-65077986-CATATACTGGAT-C is described in ClinVar as [Pathogenic]. Clinvar id is 404110.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAX | NM_002382.5 | c.211_221del | p.Ile71AlafsTer12 | frameshift_variant | 4/5 | ENST00000358664.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAX | ENST00000358664.9 | c.211_221del | p.Ile71AlafsTer12 | frameshift_variant | 4/5 | 1 | NM_002382.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary pheochromocytoma-paraganglioma Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 03, 2016 | For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, truncating variants in MAX are known to be pathogenic (PMID: 21685915, 26070438). This sequence change deletes 11 nucleotides from exon 4 of the MAX mRNA (c.211_221delATCCAGTATAT), causing a frameshift at codon 71. This creates a premature translational stop signal (p.Ile71Alafs*12) and is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at