14-65076562-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BS1_SupportingBS2
The NM_002382.5(MAX):c.397G>A(p.Ala133Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002382.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251488Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135920
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1461882Hom.: 0 Cov.: 34 AF XY: 0.0000440 AC XY: 32AN XY: 727236
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74306
ClinVar
Submissions by phenotype
Pheochromocytoma Uncertain:1Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
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Retinoblastoma Uncertain:1
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Hereditary cancer-predisposing syndrome Uncertain:1
The p.A133T variant (also known as c.397G>A), located in coding exon 5 of the MAX gene, results from a G to A substitution at nucleotide position 397. The alanine at codon 133 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Hereditary pheochromocytoma-paraganglioma Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 133 of the MAX protein (p.Ala133Thr). This variant is present in population databases (rs750459929, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with MAX-related conditions. ClinVar contains an entry for this variant (Variation ID: 239151). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt MAX function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at