rs5992854

Positions:

• chr22-17817474-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015241.3(MICAL3):​c.5187A>G​(p.Leu1729Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,613,320 control chromosomes in the GnomAD database, including 132,031 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 0.45 (17116 hom., cov: 32)
  • Exomes 𝑓: 0.39 (114915 hom.)
• Consequence: MICAL3 NM_015241.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-0.325 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICAL3	NM_015241.3	c.5187A>G	p.Leu1729Leu	synonymous_variant	26/32	ENST00000441493.7	NP_056056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICAL3	ENST00000441493.7	c.5187A>G	p.Leu1729Leu	synonymous_variant	26/32	5	NM_015241.3	ENSP00000416015.2

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68703 AN: 151870 Hom.: 17091 Cov.: 32

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.402

GnomAD3 exomes AF: 0.365 AC: 90530 AN: 247776 Hom.: 18094 AF XY: 0.363 AC XY: 48951 AN XY: 134772

Gnomad AFR exome AF: 0.651

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.205

Gnomad SAS exome AF: 0.287

Gnomad FIN exome AF: 0.417

Gnomad NFE exome AF: 0.400

Gnomad OTH exome AF: 0.383

GnomAD4 exome AF: 0.391 AC: 570714 AN: 1461332 Hom.: 114915 Cov.: 70 AF XY: 0.387 AC XY: 281512 AN XY: 726936

Gnomad4 AFR exome AF: 0.654

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.477

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.415

Gnomad4 NFE exome AF: 0.401

Gnomad4 OTH exome AF: 0.395

GnomAD4 genome AF: 0.452 AC: 68762 AN: 151988 Hom.: 17116 Cov.: 32 AF XY: 0.447 AC XY: 33188 AN XY: 74294

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.396

Alfa AF: 0.409 Hom.: 19022

Bravo AF: 0.453

Asia WGS AF: 0.276 AC: 965 AN: 3478

EpiCase AF: 0.395

EpiControl AF: 0.382

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.21

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: rs5992854; hg19: chr22-18300240; COSMIC: COSV71588389; COSMIC: COSV71588389;