rs5992854

Variant names:

• chr22-17817474-T-C
• rs5992854
• NM_015241.3:c.5187A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015241.3. 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.5187A>G	p.Leu1729Leu	synonymous	Exon 26 of 32	NP_056056.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICAL3	ENST00000441493.7	TSL:5 MANE Select	c.5187A>G	p.Leu1729Leu	synonymous	Exon 26 of 32	ENSP00000416015.2
	MICAL3	ENST00000577821.5	TSL:3	c.15A>G	p.Leu5Leu	synonymous	Exon 1 of 8	ENSP00000463882.1
	MICAL3	ENST00000672019.1		n.*2134A>G		non_coding_transcript_exon	Exon 27 of 33	ENSP00000500702.1

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

GnomAD2 exomes AF: 0.365 AC: 90530 AN: 247776 AF XY: 0.363

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 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

African (AFR) AF: 0.654 AC: 21901 AN: 33480

American (AMR) AF: 0.225 AC: 10077 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 12455 AN: 26130

East Asian (EAS) AF: 0.193 AC: 7652 AN: 39698

South Asian (SAS) AF: 0.294 AC: 25347 AN: 86244

European-Finnish (FIN) AF: 0.415 AC: 22066 AN: 53164

Middle Eastern (MID) AF: 0.358 AC: 2066 AN: 5768

European-Non Finnish (NFE) AF: 0.401 AC: 445305 AN: 1111780

Other (OTH) AF: 0.395 AC: 23845 AN: 60364

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

African (AFR) AF: 0.649 AC: 26864 AN: 41418

American (AMR) AF: 0.303 AC: 4624 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1640 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1026 AN: 5168

South Asian (SAS) AF: 0.291 AC: 1401 AN: 4818

European-Finnish (FIN) AF: 0.423 AC: 4471 AN: 10582

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27447 AN: 67940

Other (OTH) AF: 0.396 AC: 834 AN: 2104

Alfa AF: 0.422 Hom.: 30965

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.21
PhyloP100		-0.33
PromoterAI		0.0053	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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