rs4819639

Positions:

• chr22-17864361-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.2605+538G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,261,206 control chromosomes in the GnomAD database, including 39,512 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 0.23 (4193 hom., cov: 32)
  • Exomes 𝑓: 0.25 (35319 hom.)
• Consequence: MICAL3 NM_015241.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICAL3	NM_015241.3	c.2605+538G>A		intron_variant		ENST00000441493.7	NP_056056.2
MICAL3	NM_001136004.3	c.*293G>A		3_prime_UTR_variant	22/22		NP_001129476.1
MICAL3	NM_001122731.2	c.2605+538G>A		intron_variant			NP_001116203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICAL3	ENST00000441493.7	c.2605+538G>A		intron_variant		5	NM_015241.3	ENSP00000416015	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34784 AN: 151982 Hom.: 4187 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.250 AC: 277057 AN: 1109106 Hom.: 35319 Cov.: 33 AF XY: 0.249 AC XY: 131482 AN XY: 527424

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.309

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.229 AC: 34805 AN: 152100 Hom.: 4193 Cov.: 32 AF XY: 0.229 AC XY: 17019 AN XY: 74340

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.239

Alfa AF: 0.245 Hom.: 1294

Bravo AF: 0.233

Asia WGS AF: 0.212 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.6
DANN	Benign	0.75

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: rs4819639; hg19: chr22-18347127;