GeneBe

rs1553371013

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_005378.6(MYCN):​c.1226C>A​(p.Pro409Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P409L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

MYCN
NM_005378.6 missense

Scores

15
2
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.13

Publications

0 publications found
Variant links:
Genes affected
MYCN (HGNC:7559): (MYCN proto-oncogene, bHLH transcription factor) This gene is a member of the MYC family and encodes a protein with a basic helix-loop-helix (bHLH) domain. This protein is located in the nucleus and must dimerize with another bHLH protein in order to bind DNA. Amplification of this gene is associated with a variety of tumors, most notably neuroblastomas. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]
MYCN Gene-Disease associations (from GenCC):
  • Feingold syndrome type 1
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.989

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005378.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
MYCN
NM_005378.6
MANE Select
c.1226C>Ap.Pro409Gln
missense
Exon 3 of 3NP_005369.2
MYCN
NM_001293228.2
c.1226C>Ap.Pro409Gln
missense
Exon 3 of 3NP_001280157.1P04198
MYCN
NM_001293231.2
c.593C>Ap.Pro198Gln
missense
Exon 2 of 2NP_001280160.1A0A1W2PPD9

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
MYCN
ENST00000281043.4
TSL:5 MANE Select
c.1226C>Ap.Pro409Gln
missense
Exon 3 of 3ENSP00000281043.3P04198
MYCN
ENST00000885101.1
c.1226C>Ap.Pro409Gln
missense
Exon 5 of 5ENSP00000555160.1
MYCN
ENST00000930195.1
c.1226C>Ap.Pro409Gln
missense
Exon 3 of 3ENSP00000600254.1

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
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.46
D
BayesDel_noAF
Pathogenic
0.43
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.99
D
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.93
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.79
T
M_CAP
Pathogenic
0.58
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.9
H
PhyloP100
6.1
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-7.3
D
REVEL
Pathogenic
0.95
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.78
MutPred
0.88
Gain of MoRF binding (P = 0.0331)
MVP
0.93
MPC
1.8
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.92
gMVP
0.95
Mutation Taster
=18/82
disease causing

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

Other links and lift over

dbSNP: rs1553371013; hg19: chr2-16086050; API