Genetic Variant NM_015241.3:c.2605+3822A>G (chr22-17861077-T-C) – 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.2605+3822A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 984,946 control chromosomes in the GnomAD database, including 98,226 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 0.56 ( 26792 hom., cov: 32)

Exomes 𝑓: 0.41 ( 71434 hom. )

Consequence

MICAL3
NM_015241.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0640

Publications

7 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 (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MICAL3	NM_015241.3 link	c.2605+3822A>G	intron_variant	Intron 19 of 31	ENST00000441493.7	NP_056056.2
MICAL3	NM_001136004.3 link	c.*3577A>G	3_prime_UTR_variant	Exon 22 of 22		NP_001129476.1
MICAL3	NM_001122731.2 link	c.2605+3822A>G	intron_variant	Intron 18 of 19		NP_001116203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICAL3	ENST00000441493.7 link	c.2605+3822A>G		intron_variant	Intron 19 of 31	5	NM_015241.3	ENSP00000416015.2		Q7RTP6-1

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84529

AN:

151912

Hom.:

26716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.878

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.572

Gnomad ASJ

AF:

0.453

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.428

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.524

GnomAD4 exome

AF:

0.407

AC:

338977

AN:

832916

Hom.:

71434

Cov.:

AF XY:

0.407

AC XY:

156484

AN XY:

384628

show subpopulations

African (AFR)

AF:

0.921

AC:

14535

AN:

15784

American (AMR)

AF:

0.591

AC:

582

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.466

AC:

2403

AN:

5152

East Asian (EAS)

AF:

0.508

AC:

1844

AN:

3628

South Asian (SAS)

AF:

0.384

AC:

6317

AN:

16452

European-Finnish (FIN)

AF:

0.371

AC:

103

AN:

278

Middle Eastern (MID)

AF:

0.499

AC:

809

AN:

1620

European-Non Finnish (NFE)

AF:

0.394

AC:

300405

AN:

761736

Other (OTH)

AF:

0.439

AC:

11979

AN:

27282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

9936

19872

29809

39745

49681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13002

26004

39006

52008

65010

<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:

0.557

AC:

84676

AN:

152030

Hom.:

26792

Cov.:

AF XY:

0.557

AC XY:

41392

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.878

AC:

36428

AN:

41482

American (AMR)

AF:

0.573

AC:

8747

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.453

AC:

1571

AN:

3470

East Asian (EAS)

AF:

0.489

AC:

2528

AN:

5166

South Asian (SAS)

AF:

0.409

AC:

1967

AN:

4810

European-Finnish (FIN)

AF:

0.428

AC:

4517

AN:

10566

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.400

AC:

27172

AN:

67946

Other (OTH)

AF:

0.525

AC:

1111

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1630

3260

4890

6520

8150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.496

Hom.:

3561

Bravo

AF:

0.585

Asia WGS

AF:

0.483

AC:

1683

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.3

(source)

DANN

Benign

0.71

PhyloP100

-0.064

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over