6-109444235-GCTC-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting

The NM_022765.4(MICAL1):​c.3157_3159del​(p.Glu1053del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000174 in 1,613,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β˜…).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

MICAL1
NM_022765.4 inframe_deletion

Scores

Not classified

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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_022765.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MICAL1NM_022765.4 linkuse as main transcriptc.3157_3159del p.Glu1053del inframe_deletion 25/25 ENST00000358807.8 NP_073602.3
MICAL1NM_001159291.2 linkuse as main transcriptc.2899_2901del p.Glu967del inframe_deletion 24/24 NP_001152763.1
MICAL1NM_001286613.2 linkuse as main transcriptc.3214_3216del p.Glu1072del inframe_deletion 25/25 NP_001273542.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MICAL1ENST00000358807.8 linkuse as main transcriptc.3157_3159del p.Glu1053del inframe_deletion 25/251 NM_022765.4 ENSP00000351664 P2Q8TDZ2-1

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152166
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000338
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
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
250884
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.0000617
Gnomad AMR exome
AF:
0.0000868
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
AF:
0.00000890
AC:
13
AN:
1461326
Hom.:
0
AF XY:
0.00000963
AC XY:
7
AN XY:
726952
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000985
AC:
15
AN:
152284
Hom.:
0
Cov.:
33
AF XY:
0.0000806
AC XY:
6
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.000337
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
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000831

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), LabcorpMay 08, 2023In 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with MICAL1-related conditions. This variant is present in population databases (rs759905835, gnomAD 0.02%). This variant, c.3214_3216del, results in the deletion of 1 amino acid(s) of the MICAL1 protein (p.Glu1072del), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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: rs759905835; hg19: chr6-109765438; API