rs2277831

Positions:

• chr22-17816431-A-G

Variant summary

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

The NM_015241.3(MICAL3):​c.5445+259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,194 control chromosomes in the GnomAD database, including 8,441 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 0.33 (8441 hom., cov: 33)
• Consequence: MICAL3 NM_015241.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICAL3	NM_015241.3	c.5445+259T>C		intron_variant		ENST00000441493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICAL3	ENST00000441493.7	c.5445+259T>C		intron_variant		5	NM_015241.3	P1
MICAL3	ENST00000577821.5	c.274+259T>C		intron_variant		3
MICAL3	ENST00000579997.5	c.210+259T>C		intron_variant		5
MICAL3	ENST00000672019.1	c.*2392+259T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49483 AN: 152076 Hom.: 8426 Cov.: 33

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.325 AC: 49523 AN: 152194 Hom.: 8441 Cov.: 33 AF XY: 0.321 AC XY: 23856 AN XY: 74388

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.303

Alfa AF: 0.334 Hom.: 17598

Bravo AF: 0.318

Asia WGS AF: 0.180 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.22

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: rs2277831; hg19: chr22-18299197;