6-109444224-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_022765.4(MICAL1):ā€‹c.3171C>Gā€‹(p.Ser1057Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)

Consequence

MICAL1
NM_022765.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.23
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 0 ACMG points.

PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity MICA1_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.020584375).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MICAL1NM_022765.4 linkuse as main transcriptc.3171C>G p.Ser1057Arg missense_variant 25/25 ENST00000358807.8 NP_073602.3
MICAL1NM_001286613.2 linkuse as main transcriptc.3228C>G p.Ser1076Arg missense_variant 25/25 NP_001273542.1
MICAL1NM_001159291.2 linkuse as main transcriptc.2913C>G p.Ser971Arg 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.3171C>G p.Ser1057Arg missense_variant 25/251 NM_022765.4 ENSP00000351664 P2Q8TDZ2-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250746
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135790
show subpopulations
Gnomad AFR exome
AF:
0.000124
Gnomad AMR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152188
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsDec 07, 2021The c.3171C>G (p.S1057R) alteration is located in exon 25 (coding exon 24) of the MICAL1 gene. This alteration results from a C to G substitution at nucleotide position 3171, causing the serine (S) at amino acid position 1057 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
0.032
DANN
Benign
0.83
DEOGEN2
Benign
0.014
.;T;.
Eigen
Benign
-2.0
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.093
N
LIST_S2
Benign
0.74
T;T;T
M_CAP
Benign
0.0094
T
MetaRNN
Benign
0.021
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.44
.;N;.
MutationTaster
Benign
0.99
N;N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.87
N;N;.
REVEL
Benign
0.035
Sift
Benign
0.57
T;T;.
Sift4G
Benign
0.56
T;T;T
Polyphen
0.032
B;B;.
Vest4
0.22
MutPred
0.45
.;Loss of phosphorylation at S1057 (P = 0.0047);.;
MVP
0.11
MPC
0.11
ClinPred
0.037
T
GERP RS
-11
Varity_R
0.28
gMVP
0.24

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: rs145926073; hg19: chr6-109765427; API