rs1057721

Variant names:

• chr22-17861077-T-C
• rs1057721
• NM_015241.3:c.2605+3822A>G

Variant summary

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

The NM_001136004.3(MICAL3):​c.*3577A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 984,946 control chromosomes in the GnomAD database, including 98,226 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 0.56 (26792 hom., cov: 32)
  • Exomes 𝑓: 0.41 (71434 hom.)
• Consequence: MICAL3 NM_001136004.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICAL3	NM_015241.3	MANE Select	c.2605+3822A>G		intron	N/A	NP_056056.2
	MICAL3	NM_001136004.3		c.*3577A>G		3_prime_UTR	Exon 22 of 22	NP_001129476.1
	MICAL3	NM_001122731.2		c.2605+3822A>G		intron	N/A	NP_001116203.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICAL3	ENST00000441493.7	TSL:5 MANE Select	c.2605+3822A>G		intron	N/A	ENSP00000416015.2
	MICAL3	ENST00000400561.6	TSL:1	c.2605+3822A>G		intron	N/A	ENSP00000383406.2
	MICAL3	ENST00000383094.7	TSL:1	c.2605+3822A>G		intron	N/A	ENSP00000372574.3

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84529 AN: 151912 Hom.: 26716 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.524

GnomAD4 exome AF: 0.407 AC: 338977 AN: 832916 Hom.: 71434 Cov.: 33 AF XY: 0.407 AC XY: 156484 AN XY: 384628

African (AFR) AF: 0.921 AC: 14535 AN: 15784

American (AMR) AF: 0.591 AC: 582 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 2403 AN: 5152

East Asian (EAS) AF: 0.508 AC: 1844 AN: 3628

South Asian (SAS) AF: 0.384 AC: 6317 AN: 16452

European-Finnish (FIN) AF: 0.371 AC: 103 AN: 278

Middle Eastern (MID) AF: 0.499 AC: 809 AN: 1620

European-Non Finnish (NFE) AF: 0.394 AC: 300405 AN: 761736

Other (OTH) AF: 0.439 AC: 11979 AN: 27282

GnomAD4 genome AF: 0.557 AC: 84676 AN: 152030 Hom.: 26792 Cov.: 32 AF XY: 0.557 AC XY: 41392 AN XY: 74336

African (AFR) AF: 0.878 AC: 36428 AN: 41482

American (AMR) AF: 0.573 AC: 8747 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1571 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2528 AN: 5166

South Asian (SAS) AF: 0.409 AC: 1967 AN: 4810

European-Finnish (FIN) AF: 0.428 AC: 4517 AN: 10566

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27172 AN: 67946

Other (OTH) AF: 0.525 AC: 1111 AN: 2116

Alfa AF: 0.496 Hom.: 3561

Bravo AF: 0.585

Asia WGS AF: 0.483 AC: 1683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.71
PhyloP100		-0.064
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1057721; hg19: chr22-18343843;