rs1076540

chr22-17957192-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015241.3(MICAL3):c.-74-50306G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,092 control chromosomes in the GnomAD database, including 3,620 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 0.21 (3620 hom., cov: 32)
• Consequence: MICAL3 NM_015241.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICAL3	NM_015241.3	c.-74-50306G>A		intron_variant		ENST00000441493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICAL3	ENST00000441493.7	c.-74-50306G>A		intron_variant		5	NM_015241.3	P1
MICAL3	ENST00000424046.1	c.-75+43897G>A		intron_variant		4
MICAL3	ENST00000495076.5	c.-75+44201G>A		intron_variant, NMD_transcript_variant		5
MICAL3	ENST00000672019.1	c.-74-50306G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32292 AN: 151976 Hom.: 3617 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0364

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.233

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.213 AC: 32328 AN: 152092 Hom.: 3620 Cov.: 32 AF XY: 0.209 AC XY: 15550 AN XY: 74338

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0367

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.234

Alfa AF: 0.227 Hom.: 4899

Bravo AF: 0.210

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.4
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1076540; hg19: chr22-18439958;