8-127738379-G-A

Variant names:

• chr8-127738379-G-A
• rs121918684
• NM_002467.6:c.162G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_002467.6(MYC):​c.162G>A​(p.Glu54Glu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYC NM_002467.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31178427).
• BP7: Synonymous conserved (PhyloP=2.77 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002467.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYC	NM_002467.6	MANE Select	c.162G>A	p.Glu54Glu	synonymous	Exon 2 of 3	NP_002458.2	P01106-2
	MYC	NM_001354870.1		c.159G>A	p.Glu53Glu	synonymous	Exon 2 of 3	NP_001341799.1	P01106-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYC	ENST00000621592.8	TSL:1 MANE Select	c.162G>A	p.Glu54Glu	synonymous	Exon 2 of 3	ENSP00000478887.2	P01106-2
	MYC	ENST00000524013.2	TSL:1	c.159G>A	p.Glu53Glu	synonymous	Exon 2 of 3	ENSP00000430235.2	P01106-3
	MYC	ENST00000377970.6	TSL:1	c.117G>A	p.Glu39Glu	synonymous	Exon 2 of 3	ENSP00000367207.3	P01106-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.97
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.97	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.56	T
PhyloP100		2.8
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.17
MutPred		0.15		Loss of phosphorylation at S28 (P = 0.0011)
MVP		0.76
ClinPred		0.36	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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

Other links and lift over

dbSNP: rs121918684; hg19: chr8-128750625; COSMIC: COSV52367980; COSMIC: COSV52367980;