rs775522201

Positions:

• chr8-127738393-C-A
• chr8-127738393-C-G
• chr8-127738393-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002467.6(MYC):​c.176C>A​(p.Ala59Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYC NM_002467.6 missense
• 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]

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYC	NM_002467.6	c.176C>A	p.Ala59Glu	missense_variant	2/3	ENST00000621592.8	NP_002458.2
MYC	NM_001354870.1	c.173C>A	p.Ala58Glu	missense_variant	2/3		NP_001341799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYC	ENST00000621592.8	c.176C>A	p.Ala59Glu	missense_variant	2/3	1	NM_002467.6	ENSP00000478887	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461696 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727142

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	29
DANN	Benign	0.95
DEOGEN2	Benign	0.32	.;T;T;T;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D
M_CAP	Uncertain	0.089	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D
MetaSVM	Uncertain	-0.023	T
MutationAssessor	Pathogenic	3.1	.;.;.;M;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.5	D;D;.;.;N;.
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D;D;.;.;D;.
Sift4G	Uncertain	0.010	D;D;D;D;D;D
Polyphen		1.0	.;.;.;D;.;.
Vest4		0.60
MutPred		0.57		Gain of relative solvent accessibility (P = 0.0507);.;.;Gain of relative solvent accessibility (P = 0.0507);.;.;
MVP		0.63
ClinPred		0.99	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.67
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-128750639;