Variant 6-109444250-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000358807.8(MICAL1):c.3145C>T(p.Arg1049Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000725 in 1,613,678 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1049H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0039 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00039 ( 3 hom. )

Consequence

MICAL1
ENST00000358807.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.61

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]

MICAL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045151412).

BP6

Variant 6-109444250-G-A is Benign according to our data. Variant chr6-109444250-G-A is described in ClinVar as [Benign]. Clinvar id is 782250.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MICAL1	NM_022765.4 linkuse as main transcript	c.3145C>T	p.Arg1049Cys	missense_variant	25/25	ENST00000358807.8	NP_073602.3
MICAL1	NM_001286613.2 linkuse as main transcript	c.3202C>T	p.Arg1068Cys	missense_variant	25/25		NP_001273542.1
MICAL1	NM_001159291.2 linkuse as main transcript	c.2887C>T	p.Arg963Cys	missense_variant	24/24		NP_001152763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICAL1	ENST00000358807.8 linkuse as main transcript	c.3145C>T	p.Arg1049Cys	missense_variant	25/25	1	NM_022765.4	ENSP00000351664	P2	Q8TDZ2-1

Frequencies

GnomAD3 genomes

AF:

0.00392

AC:

597

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000952

AC:

239

AN:

250984

Hom.:

AF XY:

0.000574

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.0132

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000390

AC:

570

AN:

1461388

Hom.:

Cov.:

AF XY:

0.000331

AC XY:

241

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.0148

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.00394

AC:

600

AN:

152290

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

288

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0141

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.00431

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00121

AC:

147

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

.;T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.041

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.89

D;D;D

MetaRNN

Benign

0.0045

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

.;L;.

MutationTaster

Benign

0.76

D;D;D

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.4

N;N;.

REVEL

Benign

0.044

Sift

Uncertain

0.0060

D;D;.

Sift4G

Uncertain

0.053

T;D;D

Polyphen

0.43

B;B;.

Vest4

0.28

MVP

0.53

MPC

0.13

ClinPred

0.038

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.18

gMVP

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over