chr14-65101552-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_002382.5(MAX):c.57A>C(p.Gln19His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q19L) has been classified as Likely benign.
Frequency
Consequence
NM_002382.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAX | NM_002382.5 | c.57A>C | p.Gln19His | missense_variant | 2/5 | ENST00000358664.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAX | ENST00000358664.9 | c.57A>C | p.Gln19His | missense_variant | 2/5 | 1 | NM_002382.5 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1458582Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725760
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 15, 2024 | The p.Q19H variant (also known as c.57A>C), located in coding exon 2 of the MAX gene, results from an A to C substitution at nucleotide position 57. The glutamine at codon 19 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Hereditary pheochromocytoma-paraganglioma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 27, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1035736). This variant has not been reported in the literature in individuals affected with MAX-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 19 of the MAX protein (p.Gln19His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at