8-127738379-G-C

Position:

• chr8-127738379-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_002467.6(MYC):​c.162G>C​(p.Glu54Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYC NM_002467.6 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.77

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-127738379-G-C is Pathogenic according to our data. Variant chr8-127738379-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 12576.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.22626844). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYC	NM_002467.6	c.162G>C	p.Glu54Asp	missense_variant	2/3	ENST00000621592.8	NP_002458.2
MYC	NM_001354870.1	c.159G>C	p.Glu53Asp	missense_variant	2/3		NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8	c.162G>C	p.Glu54Asp	missense_variant	2/3	1	NM_002467.6	ENSP00000478887	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Burkitt lymphoma Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 1993

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.23	.;T;T;T;.;.
Eigen	Benign	0.076
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.67	T;T;T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	.;.;.;L;.;.
MutationTaster	Benign	0.76	A
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.63	N;N;.;.;N;.
REVEL	Benign	0.18
Sift	Benign	0.15	T;T;.;.;T;.
Sift4G	Benign	0.59	T;T;T;T;T;T
Polyphen		0.22	.;.;.;B;.;.
Vest4		0.38
MutPred		0.27		Loss of glycosylation at P42 (P = 0.1441);.;.;Loss of glycosylation at P42 (P = 0.1441);.;.;
MVP		0.56
ClinPred		0.44	T
GERP RS		3.9
Varity_R		0.17
gMVP		0.15

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

LitVar

Other links and lift over

dbSNP: rs121918684; hg19: chr8-128750625; COSMIC: COSV52367472; COSMIC: COSV52367472;