6-109444244-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022765.4(MICAL1):c.3151C>T(p.Gln1051Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000149 in 1,613,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
MICAL1
NM_022765.4 stop_gained
NM_022765.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 7.14
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 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 |
---|---|---|---|---|---|---|---|---|
MICAL1 | NM_022765.4 | c.3151C>T | p.Gln1051Ter | stop_gained | 25/25 | ENST00000358807.8 | NP_073602.3 | |
MICAL1 | NM_001286613.2 | c.3208C>T | p.Gln1070Ter | stop_gained | 25/25 | NP_001273542.1 | ||
MICAL1 | NM_001159291.2 | c.2893C>T | p.Gln965Ter | stop_gained | 24/24 | NP_001152763.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MICAL1 | ENST00000358807.8 | c.3151C>T | p.Gln1051Ter | stop_gained | 25/25 | 1 | NM_022765.4 | ENSP00000351664 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152164Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250958Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135854
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461376Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 726990
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74332
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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 01, 2023 | This sequence change creates a premature translational stop signal (p.Gln1070*) in the MICAL1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 17 amino acid(s) of the MICAL1 protein. This variant is present in population databases (rs757758020, gnomAD 0.002%). 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: 1503366). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D;D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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