8-127738995-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_002467.6(MYC):c.778C>G(p.Pro260Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,370,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

MYC
NM_002467.6 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.35

Publications

9 publications found

Variant links:

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]

MYC links:

CASC11 (HGNC:48939): (cancer susceptibility 11)

CASC11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 11 curated pathogenic missense variants (we use a threshold of 10). The gene has 2 curated benign missense variants. Gene score misZ: 1.2227 (below the threshold of 3.09). Trascript score misZ: 1.518 (below the threshold of 3.09). GenCC associations: The gene is linked to Burkitt lymphoma.

BP4

Computational evidence support a benign effect (MetaRNN=0.22519168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYC	NM_002467.6 link	c.778C>G	p.Pro260Ala	missense_variant	Exon 2 of 3	ENST00000621592.8	NP_002458.2
MYC	NM_001354870.1 link	c.775C>G	p.Pro259Ala	missense_variant	Exon 2 of 3		NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8 link	c.778C>G	p.Pro260Ala	missense_variant	Exon 2 of 3	1	NM_002467.6	ENSP00000478887.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.30e-7

AC:

AN:

1370348

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

673728

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30828

American (AMR)

AF:

0.00

AC:

AN:

32138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21658

East Asian (EAS)

AF:

0.00

AC:

AN:

38714

South Asian (SAS)

AF:

0.00

AC:

AN:

74322

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5420

European-Non Finnish (NFE)

AF:

9.31e-7

AC:

AN:

1074104

Other (OTH)

AF:

0.00

AC:

AN:

56818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Neoplasm

Pathogenic:1

Jul 14, 2015

Database of Curated Mutations (DoCM)

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

.;T;T;.;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

D;D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.23

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

.;.;L;.;.

PhyloP100

2.4

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.7

N;.;.;N;.

REVEL

Benign

0.064

Sift

Uncertain

0.0040

D;.;.;D;.

Sift4G

Benign

0.16

T;T;T;T;T

Polyphen

0.65

.;.;P;.;.

Vest4

0.27

MutPred

0.36

Loss of catalytic residue at P245 (P = 0.0148);.;Loss of catalytic residue at P245 (P = 0.0148);.;.;

MVP

0.52

ClinPred

0.37

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

3.1

Varity_R

0.33

gMVP

0.40

Mutation Taster

=84/16

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over