chr8-127738393-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM5
The NM_002467.6(MYC):c.176C>G(p.Ala59Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A59V) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 33)
Consequence
MYC
NM_002467.6 missense
NM_002467.6 missense
Scores
1
8
8
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.12
Genes affected
MYC (HGNC:7553): (MYC proto-oncogene, bHLH transcription factor) This gene is a proto-oncogene and encodes a nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. The encoded protein forms a heterodimer with the related transcription factor MAX. This complex binds to the E box DNA consensus sequence and regulates the transcription of specific target genes. Amplification of this gene is frequently observed in numerous human cancers. Translocations involving this gene are associated with Burkitt lymphoma and multiple myeloma in human patients. There is evidence to show that translation initiates both from an upstream, in-frame non-AUG (CUG) and a downstream AUG start site, resulting in the production of two isoforms with distinct N-termini. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr8-127738393-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 376299.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYC | NM_002467.6 | c.176C>G | p.Ala59Gly | missense_variant | 2/3 | ENST00000621592.8 | |
MYC | NM_001354870.1 | c.173C>G | p.Ala58Gly | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYC | ENST00000621592.8 | c.176C>G | p.Ala59Gly | missense_variant | 2/3 | 1 | NM_002467.6 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;.;N;.
REVEL
Benign
Sift
Uncertain
D;D;.;.;T;.
Sift4G
Benign
T;D;D;T;D;D
Polyphen
1.0
.;.;.;D;.;.
Vest4
MutPred
Gain of catalytic residue at A44 (P = 0.0691);.;.;Gain of catalytic residue at A44 (P = 0.0691);.;.;
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
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