chr6-109444232-T-C

Variant summary

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

The NM_022765.4(MICAL1):ā€‹c.3163A>Gā€‹(p.Arg1055Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,350 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.000017 ( 1 hom. )

Consequence

MICAL1
NM_022765.4 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38
Variant links:
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]

Genome browser will be placed here

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
MICAL1NM_022765.4 linkuse as main transcriptc.3163A>G p.Arg1055Gly missense_variant 25/25 ENST00000358807.8 NP_073602.3
MICAL1NM_001286613.2 linkuse as main transcriptc.3220A>G p.Arg1074Gly missense_variant 25/25 NP_001273542.1
MICAL1NM_001159291.2 linkuse as main transcriptc.2905A>G p.Arg969Gly missense_variant 24/24 NP_001152763.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MICAL1ENST00000358807.8 linkuse as main transcriptc.3163A>G p.Arg1055Gly missense_variant 25/251 NM_022765.4 ENSP00000351664 P2Q8TDZ2-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250910
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135824
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1461350
Hom.:
1
Cov.:
33
AF XY:
0.0000248
AC XY:
18
AN XY:
726968
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 27, 2023This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1074 of the MICAL1 protein (p.Arg1074Gly). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MICAL1-related conditions. 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.10
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
.;T;.
Eigen
Uncertain
0.27
Eigen_PC
Benign
0.099
FATHMM_MKL
Benign
0.65
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.076
D
MetaRNN
Uncertain
0.66
D;D;D
MetaSVM
Benign
-0.56
T
MutationAssessor
Pathogenic
3.5
.;H;.
MutationTaster
Benign
0.72
N;N;N
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-2.7
D;D;.
REVEL
Uncertain
0.43
Sift
Uncertain
0.0020
D;D;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.63
MutPred
0.59
.;Loss of stability (P = 0.0483);.;
MVP
0.60
MPC
0.52
ClinPred
0.97
D
GERP RS
-2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.88
gMVP
0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1230451323; hg19: chr6-109765435; API