8-127738888-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002467.6(MYC):c.671C>T(p.Ala224Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,611,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000041 ( 0 hom. )
Consequence
MYC
NM_002467.6 missense
NM_002467.6 missense
Scores
3
14
Clinical Significance
Conservation
PhyloP100: 5.10
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 Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.14173567).
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYC | NM_002467.6 | c.671C>T | p.Ala224Val | missense_variant | 2/3 | ENST00000621592.8 | |
MYC | NM_001354870.1 | c.668C>T | p.Ala223Val | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYC | ENST00000621592.8 | c.671C>T | p.Ala224Val | missense_variant | 2/3 | 1 | NM_002467.6 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000325 AC: 8AN: 245776Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134012
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GnomAD4 exome AF: 0.0000411 AC: 60AN: 1459768Hom.: 0 Cov.: 32 AF XY: 0.0000386 AC XY: 28AN XY: 726262
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 19, 2023 | The c.671C>T (p.A224V) alteration is located in exon 2 (coding exon 2) of the MYC gene. This alteration results from a C to T substitution at nucleotide position 671, causing the alanine (A) at amino acid position 224 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.;N;.
REVEL
Benign
Sift
Uncertain
D;.;.;D;.
Sift4G
Benign
T;T;T;T;T
Polyphen
0.19
.;.;B;.;.
Vest4
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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