dbSNP rs4819639: MICAL3:c.2605+538G>A (chr22-17864361-C-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_001136004.3(MICAL3):c.*293G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,261,206 control chromosomes in the GnomAD database, including 39,512 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 0.23 ( 4193 hom., cov: 32)

Exomes 𝑓: 0.25 ( 35319 hom. )

Consequence

MICAL3
NM_001136004.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.682

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:

Genome browser will be placed here

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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136004.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MICAL3	NM_015241.3	MANE Select	c.2605+538G>A	intron	N/A	NP_056056.2	Q7RTP6-1
MICAL3	NM_001136004.3		c.*293G>A	3_prime_UTR	Exon 22 of 22	NP_001129476.1	Q7RTP6-5
MICAL3	NM_001122731.2		c.2605+538G>A	intron	N/A	NP_001116203.1	Q7RTP6-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MICAL3	ENST00000441493.7	TSL:5 MANE Select	c.2605+538G>A	intron	N/A	ENSP00000416015.2	Q7RTP6-1
MICAL3	ENST00000400561.6	TSL:1	c.2605+538G>A	intron	N/A	ENSP00000383406.2	Q7RTP6-4
MICAL3	ENST00000383094.7	TSL:1	c.2605+538G>A	intron	N/A	ENSP00000372574.3	Q7RTP6-2

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34784

AN:

151982

Hom.:

4187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.241

GnomAD4 exome

AF:

0.250

AC:

277057

AN:

1109106

Hom.:

35319

Cov.:

AF XY:

0.249

AC XY:

131482

AN XY:

527424

show subpopulations

African (AFR)

AF:

0.154

AC:

3848

AN:

24938

American (AMR)

AF:

0.274

AC:

3537

AN:

12932

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

4413

AN:

14292

East Asian (EAS)

AF:

0.319

AC:

7108

AN:

22288

South Asian (SAS)

AF:

0.172

AC:

7768

AN:

45096

European-Finnish (FIN)

AF:

0.241

AC:

3780

AN:

15682

Middle Eastern (MID)

AF:

0.278

AC:

804

AN:

2894

European-Non Finnish (NFE)

AF:

0.253

AC:

234820

AN:

927284

Other (OTH)

AF:

0.251

AC:

10979

AN:

43700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

10712

21424

32136

42848

53560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9258

18516

27774

37032

46290

<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:

0.229

AC:

34805

AN:

152100

Hom.:

4193

Cov.:

AF XY:

0.229

AC XY:

17019

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.158

AC:

6542

AN:

41504

American (AMR)

AF:

0.251

AC:

3837

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1051

AN:

3468

East Asian (EAS)

AF:

0.319

AC:

1645

AN:

5160

South Asian (SAS)

AF:

0.173

AC:

832

AN:

4816

European-Finnish (FIN)

AF:

0.240

AC:

2542

AN:

10572

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.257

AC:

17481

AN:

67970

Other (OTH)

AF:

0.239

AC:

504

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1375

2751

4126

5502

6877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.245

Hom.:

1563

Bravo

AF:

0.233

Asia WGS

AF:

0.212

AC:

738

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.6

(source)

DANN

Benign

0.75

PhyloP100

0.68

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