22-17983394-A-G

Variant names:

• chr22-17983394-A-G
• rs387399
• NM_015241.3:c.-75+40887T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015241.3(MICAL3):​c.-75+40887T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 150,536 control chromosomes in the GnomAD database, including 26,519 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 0.59 (26507 hom., cov: 30)
  • Exomes 𝑓: 0.49 (12 hom.)
• Consequence: MICAL3 NM_015241.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 4 publications found

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]

ENSG00000235445 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICAL3	NM_015241.3	MANE Select	c.-75+40887T>C		intron	N/A	NP_056056.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICAL3	ENST00000441493.7	TSL:5 MANE Select	c.-75+40887T>C		intron	N/A	ENSP00000416015.2
	ENSG00000235445	ENST00000429618.1	TSL:5	n.226T>C		non_coding_transcript_exon	Exon 1 of 2
	MICAL3	ENST00000424046.1	TSL:4	c.-75+17695T>C		intron	N/A	ENSP00000406193.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 88427 AN: 150334 Hom.: 26460 Cov.: 30

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.632

GnomAD4 exome AF: 0.488 AC: 42 AN: 86 Hom.: 12 Cov.: 0 AF XY: 0.517 AC XY: 31 AN XY: 60

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 7 AN: 14

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.516 AC: 33 AN: 64

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.588 AC: 88537 AN: 150450 Hom.: 26507 Cov.: 30 AF XY: 0.585 AC XY: 43027 AN XY: 73498

African (AFR) AF: 0.695 AC: 28230 AN: 40612

American (AMR) AF: 0.627 AC: 9498 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1868 AN: 3422

East Asian (EAS) AF: 0.564 AC: 2906 AN: 5152

South Asian (SAS) AF: 0.490 AC: 2337 AN: 4770

European-Finnish (FIN) AF: 0.505 AC: 5285 AN: 10456

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36416 AN: 67598

Other (OTH) AF: 0.630 AC: 1320 AN: 2096

Alfa AF: 0.565 Hom.: 3054

Bravo AF: 0.608

Asia WGS AF: 0.527 AC: 1777 AN: 3366

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.44
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs387399; hg19: chr22-18466160;