chr6-109444270-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022765.4(MICAL1):ā€‹c.3125A>Gā€‹(p.Asn1042Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,158 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)

Consequence

MICAL1
NM_022765.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3109437).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MICAL1NM_022765.4 linkuse as main transcriptc.3125A>G p.Asn1042Ser missense_variant 25/25 ENST00000358807.8 NP_073602.3
MICAL1NM_001286613.2 linkuse as main transcriptc.3182A>G p.Asn1061Ser missense_variant 25/25 NP_001273542.1
MICAL1NM_001159291.2 linkuse as main transcriptc.2867A>G p.Asn956Ser 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.3125A>G p.Asn1042Ser missense_variant 25/251 NM_022765.4 ENSP00000351664 P2Q8TDZ2-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152158
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152158
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
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), LabcorpApr 25, 2022In 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. This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1061 of the MICAL1 protein (p.Asn1061Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MICAL1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.046
.;T;.
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.31
T;T;T
MetaSVM
Benign
-0.80
T
MutationAssessor
Pathogenic
3.0
.;M;.
MutationTaster
Benign
0.90
N;N;N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.2
N;N;.
REVEL
Benign
0.15
Sift
Benign
0.031
D;T;.
Sift4G
Benign
0.093
T;T;T
Polyphen
0.97
D;P;.
Vest4
0.42
MutPred
0.31
.;Gain of phosphorylation at N1042 (P = 0.0554);.;
MVP
0.62
MPC
0.19
ClinPred
0.83
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.24
gMVP
0.055

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: rs1775104445; hg19: chr6-109765473; API