chr5-113049223-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001085377.2(MCC):c.2525C>T(p.Thr842Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000657 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000065 ( 0 hom. )
Consequence
MCC
NM_001085377.2 missense
NM_001085377.2 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 4.74
Genes affected
MCC (HGNC:6935): (MCC regulator of WNT signaling pathway) This gene is a candidate colorectal tumor suppressor gene that is thought to negatively regulate cell cycle progression. The orthologous gene in the mouse expresses a phosphoprotein associated with the plasma membrane and membrane organelles, and overexpression of the mouse protein inhibits entry into S phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
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 | UniProt |
---|---|---|---|---|---|---|---|
MCC | NM_001085377.2 | c.2525C>T | p.Thr842Met | missense_variant | 16/19 | ENST00000408903.7 | |
MCC | NM_002387.3 | c.1955C>T | p.Thr652Met | missense_variant | 14/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCC | ENST00000408903.7 | c.2525C>T | p.Thr842Met | missense_variant | 16/19 | 2 | NM_001085377.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152242Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000878 AC: 22AN: 250682Hom.: 0 AF XY: 0.0000812 AC XY: 11AN XY: 135548
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GnomAD4 exome AF: 0.0000650 AC: 95AN: 1461602Hom.: 0 Cov.: 39 AF XY: 0.0000701 AC XY: 51AN XY: 727084
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GnomAD4 genome AF: 0.0000722 AC: 11AN: 152360Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74504
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 03, 2022 | The c.2525C>T (p.T842M) alteration is located in exon 16 (coding exon 16) of the MCC gene. This alteration results from a C to T substitution at nucleotide position 2525, causing the threonine (T) at amino acid position 842 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;.
REVEL
Benign
Sift
Uncertain
D;D;D;.
Sift4G
Uncertain
D;D;D;D
Polyphen
D;.;D;.
Vest4
MVP
MPC
0.34
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at