dbSNP rs5992854: MICAL3:p.Leu1729Leu (chr22-17817474-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015241.3(MICAL3):c.5187A>G(p.Leu1729Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,613,320 control chromosomes in the GnomAD database, including 132,031 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 0.45 ( 17116 hom., cov: 32)

Exomes 𝑓: 0.39 ( 114915 hom. )

Consequence

MICAL3
NM_015241.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.325

Publications

14 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP7

Synonymous conserved (PhyloP=-0.325 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICAL3	NM_015241.3 link	c.5187A>G	p.Leu1729Leu	synonymous_variant	Exon 26 of 32	ENST00000441493.7	NP_056056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICAL3	ENST00000441493.7 link	c.5187A>G	p.Leu1729Leu	synonymous_variant	Exon 26 of 32	5	NM_015241.3	ENSP00000416015.2		Q7RTP6-1

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68703

AN:

151870

Hom.:

17091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.648

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.423

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.404

Gnomad OTH

AF:

0.402

GnomAD2 exomes

AF:

0.365

AC:

90530

AN:

247776

AF XY:

0.363

show subpopulations

Gnomad AFR exome

AF:

0.651

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.473

Gnomad EAS exome

AF:

0.205

Gnomad FIN exome

AF:

0.417

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.383

GnomAD4 exome

AF:

0.391

AC:

570714

AN:

1461332

Hom.:

114915

Cov.:

AF XY:

0.387

AC XY:

281512

AN XY:

726936

show subpopulations

African (AFR)

AF:

0.654

AC:

21901

AN:

33480

American (AMR)

AF:

0.225

AC:

10077

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.477

AC:

12455

AN:

26130

East Asian (EAS)

AF:

0.193

AC:

7652

AN:

39698

South Asian (SAS)

AF:

0.294

AC:

25347

AN:

86244

European-Finnish (FIN)

AF:

0.415

AC:

22066

AN:

53164

Middle Eastern (MID)

AF:

0.358

AC:

2066

AN:

5768

European-Non Finnish (NFE)

AF:

0.401

AC:

445305

AN:

1111780

Other (OTH)

AF:

0.395

AC:

23845

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

23229

46458

69686

92915

116144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13710

27420

41130

54840

68550

<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:

0.452

AC:

68762

AN:

151988

Hom.:

17116

Cov.:

AF XY:

0.447

AC XY:

33188

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.649

AC:

26864

AN:

41418

American (AMR)

AF:

0.303

AC:

4624

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

1640

AN:

3470

East Asian (EAS)

AF:

0.199

AC:

1026

AN:

5168

South Asian (SAS)

AF:

0.291

AC:

1401

AN:

4818

European-Finnish (FIN)

AF:

0.423

AC:

4471

AN:

10582

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.404

AC:

27447

AN:

67940

Other (OTH)

AF:

0.396

AC:

834

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1827

3654

5482

7309

9136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<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:

0.422

Hom.:

30965

Bravo

AF:

0.453

Asia WGS

AF:

0.276

AC:

965

AN:

3478

EpiCase

AF:

0.395

EpiControl

AF:

0.382

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.18

(source)

DANN

Benign

0.21

PhyloP100

-0.33

PromoterAI

0.0053

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over