Genetic Variant NM_015241.3:c.5445+929C>A (chr22-17815761-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015241.3(MICAL3):c.5445+929C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,236 control chromosomes in the GnomAD database, including 7,294 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7289 hom., cov: 33)

Exomes 𝑓: 0.29 ( 5 hom. )

Consequence

MICAL3
NM_015241.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0160

Publications

4 publications found

Variant links:

Genes affected

MICAL3 (HGNC:24694): (microtubule associated monooxygenase, calponin and LIM domain containing 3) Enables actin binding activity. Involved in actin filament depolymerization. Located in several cellular components, including Flemming body; intercellular bridge; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MICAL3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015241.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICAL3	NM_015241.3	MANE Select	c.5445+929C>A		intron	N/A	NP_056056.2	Q7RTP6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MICAL3	ENST00000441493.7	TSL:5 MANE Select	c.5445+929C>A	intron	N/A	ENSP00000416015.2	Q7RTP6-1
MICAL3	ENST00000577821.5	TSL:3	c.273+929C>A	intron	N/A	ENSP00000463882.1	J3QQT0
MICAL3	ENST00000579997.5	TSL:5	c.210+929C>A	intron	N/A	ENSP00000462107.1	J3KRP8

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45924

AN:

151982

Hom.:

7288

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.292

GnomAD4 exome

AF:

0.287

AC:

AN:

136

Hom.:

AF XY:

0.255

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.389

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.281

AC:

AN:

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.302

AC:

45939

AN:

152100

Hom.:

7289

Cov.:

AF XY:

0.299

AC XY:

22242

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.273

AC:

11343

AN:

41484

American (AMR)

AF:

0.239

AC:

3645

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

1396

AN:

3470

East Asian (EAS)

AF:

0.103

AC:

533

AN:

5186

South Asian (SAS)

AF:

0.217

AC:

1047

AN:

4826

European-Finnish (FIN)

AF:

0.349

AC:

3691

AN:

10580

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.343

AC:

23323

AN:

67964

Other (OTH)

AF:

0.288

AC:

608

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1636

3272

4909

6545

8181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

466

932

1398

1864

2330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.319

Hom.:

5774

Bravo

AF:

0.292

Asia WGS

AF:

0.162

AC:

563

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.6

(source)

DANN

Benign

0.66

PhyloP100

0.016

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over