rs370238588
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_002382.5(MAX):c.375C>T(p.Asn125=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000359 in 1,614,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000037 ( 0 hom. )
Consequence
MAX
NM_002382.5 synonymous
NM_002382.5 synonymous
Scores
2
3
8
Clinical Significance
Conservation
PhyloP100: 5.23
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 Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.19279382).
BP6
Variant 14-65076584-G-A is Benign according to our data. Variant chr14-65076584-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 412780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000263 (4/152254) while in subpopulation SAS AF= 0.000415 (2/4822). AF 95% confidence interval is 0.000073. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 54 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAX | NM_002382.5 | c.375C>T | p.Asn125= | synonymous_variant | 5/5 | ENST00000358664.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAX | ENST00000358664.9 | c.375C>T | p.Asn125= | synonymous_variant | 5/5 | 1 | NM_002382.5 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152136Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251458Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135910
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GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461892Hom.: 0 Cov.: 34 AF XY: 0.0000495 AC XY: 36AN XY: 727248
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74452
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 28, 2015 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
MAX-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 22, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hereditary pheochromocytoma-paraganglioma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;N
PROVEAN
Pathogenic
D
REVEL
Uncertain
Polyphen
P
Vest4
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at