22-18022035-T-G

Variant names:

• chr22-18022035-T-G
• rs390495
• NM_015241.3:c.-75+2246A>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+2246A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,010 control chromosomes in the GnomAD database, including 34,983 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 0.67 (34983 hom., cov: 31)
• Consequence: MICAL3 NM_015241.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905
• Publications: 7 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 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+2246A>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+2246A>C		intron	N/A	ENSP00000416015.2
	MICAL3	ENST00000672019.1		n.-75+2246A>C		intron	N/A	ENSP00000500702.1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101347 AN: 151892 Hom.: 34938 Cov.: 31

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.656

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.667 AC: 101461 AN: 152010 Hom.: 34983 Cov.: 31 AF XY: 0.665 AC XY: 49400 AN XY: 74278

African (AFR) AF: 0.851 AC: 35270 AN: 41468

American (AMR) AF: 0.660 AC: 10071 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2044 AN: 3466

East Asian (EAS) AF: 0.776 AC: 4010 AN: 5166

South Asian (SAS) AF: 0.527 AC: 2533 AN: 4810

European-Finnish (FIN) AF: 0.584 AC: 6163 AN: 10560

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39307 AN: 67966

Other (OTH) AF: 0.658 AC: 1384 AN: 2104

Alfa AF: 0.610 Hom.: 109132

Bravo AF: 0.686

Asia WGS AF: 0.650 AC: 2257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.63
DANN	Benign	0.76
PhyloP100		-0.91
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: rs390495; hg19: chr22-18504801;