22-17791212-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The NM_015241.3(MICAL3):c.5740C>T(p.Leu1914=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00184 in 1,613,784 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L1914L) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (4 hom.)
• Consequence: MICAL3 NM_015241.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.91

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BP6: Variant 22-17791212-G-A is Benign according to our data. Variant chr22-17791212-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICAL3	NM_015241.3	c.5740C>T	p.Leu1914=	synonymous_variant	30/32	ENST00000441493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICAL3	ENST00000441493.7	c.5740C>T	p.Leu1914=	synonymous_variant	30/32	5	NM_015241.3	P1
	ENST00000476405.1	n.979C>T		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 177 AN: 152234 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00197

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00134 AC: 333 AN: 248524 Hom.: 0 AF XY: 0.00132 AC XY: 178 AN XY: 134952

Gnomad AFR exome AF: 0.000388

Gnomad AMR exome AF: 0.0000871

Gnomad ASJ exome AF: 0.00219

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00130

Gnomad NFE exome AF: 0.00237

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00191 AC: 2795 AN: 1461432 Hom.: 4 Cov.: 32 AF XY: 0.00183 AC XY: 1329 AN XY: 726986

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00233

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00154

Gnomad4 NFE exome AF: 0.00230

Gnomad4 OTH exome AF: 0.00134

GnomAD4 genome AF: 0.00116 AC: 176 AN: 152352 Hom.: 2 Cov.: 33 AF XY: 0.000940 AC XY: 70 AN XY: 74500

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00195

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00157 Hom.: 2

Bravo AF: 0.00112

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00213

EpiControl AF: 0.00202

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

MICAL3: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
Cadd	Benign	17
Dann	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs61743624; hg19: chr22-18273978; COSMIC: COSV52811098; COSMIC: COSV52811098;