rs1057721

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICAL3	NM_015241.3	c.2605+3822A>G		intron_variant	Intron 19 of 31	ENST00000441493.7	NP_056056.2
MICAL3	NM_001136004.3	c.*3577A>G		3_prime_UTR_variant	Exon 22 of 22		NP_001129476.1
MICAL3	NM_001122731.2	c.2605+3822A>G		intron_variant	Intron 18 of 19		NP_001116203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICAL3	ENST00000441493.7	c.2605+3822A>G		intron_variant	Intron 19 of 31	5	NM_015241.3	ENSP00000416015.2

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

Gnomad4 AFR exome AF: 0.921

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.466

Gnomad4 EAS exome AF: 0.508

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.371

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.439

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

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.525

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057721; hg19: chr22-18343843;