22-18022035-T-G

Position:

• chr22-18022035-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICAL3	NM_015241.3	c.-75+2246A>C		intron_variant		ENST00000441493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICAL3	ENST00000441493.7	c.-75+2246A>C		intron_variant		5	NM_015241.3	P1
MICAL3	ENST00000672019.1	c.-75+2246A>C		intron_variant, NMD_transcript_variant

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

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.658

Alfa AF: 0.595 Hom.: 43588

Bravo AF: 0.686

Asia WGS AF: 0.650 AC: 2257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.63
DANN	Benign	0.76

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: rs390495; hg19: chr22-18504801;