chr6-109444234-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_022765.4(MICAL1):c.3161G>A(p.Arg1054His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
MICAL1
NM_022765.4 missense
NM_022765.4 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 2.94
Genes affected
MICAL1 (HGNC:20619): (microtubule associated monooxygenase, calponin and LIM domain containing 1) This gene encodes an enzyme that oxidizes methionine residues on actin, thereby promoting depolymerization of actin filaments. This protein interacts with and regulates signalling by NEDD9/CAS-L (neural precursor cell expressed, developmentally down-regulated 9). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.184387).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MICAL1 | NM_022765.4 | c.3161G>A | p.Arg1054His | missense_variant | 25/25 | ENST00000358807.8 | NP_073602.3 | |
MICAL1 | NM_001286613.2 | c.3218G>A | p.Arg1073His | missense_variant | 25/25 | NP_001273542.1 | ||
MICAL1 | NM_001159291.2 | c.2903G>A | p.Arg968His | missense_variant | 24/24 | NP_001152763.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MICAL1 | ENST00000358807.8 | c.3161G>A | p.Arg1054His | missense_variant | 25/25 | 1 | NM_022765.4 | ENSP00000351664 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152220Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 250908Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135836
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GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461322Hom.: 0 Cov.: 33 AF XY: 0.0000261 AC XY: 19AN XY: 726954
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74358
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 11, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1073 of the MICAL1 protein (p.Arg1073His). This variant is present in population databases (rs139807207, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MICAL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2074718). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Uncertain
D;D;.
Sift4G
Benign
T;D;D
Polyphen
D;D;.
Vest4
MVP
MPC
0.45
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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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