rs387399

chr22-17983394-A-Gchr22-17983394-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICAL3	NM_015241.3	c.-75+40887T>C		intron_variant		ENST00000441493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICAL3	ENST00000441493.7	c.-75+40887T>C		intron_variant		5	NM_015241.3	P1
	ENST00000429618.1	n.226T>C		non_coding_transcript_exon_variant	1/2	5

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

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.516

Gnomad4 OTH exome AF: 0.250

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

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.630

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.37
Dann	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs387399; hg19: chr22-18466160;