22-17910798-C-T

Variant names:

• chr22-17910798-C-T
• rs4819648
• NM_015241.3:c.-74-3912G>A

Variant summary

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

The NM_015241.3(MICAL3):​c.-74-3912G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,184 control chromosomes in the GnomAD database, including 2,727 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 0.19 (2727 hom., cov: 32)
• Consequence: MICAL3 NM_015241.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICAL3	NM_015241.3	c.-74-3912G>A		intron_variant	Intron 1 of 31	ENST00000441493.7	NP_056056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICAL3	ENST00000441493.7	c.-74-3912G>A		intron_variant	Intron 1 of 31	5	NM_015241.3	ENSP00000416015.2
MICAL3	ENST00000424046.1	c.-74-3912G>A		intron_variant	Intron 1 of 2	4		ENSP00000406193.1
MICAL3	ENST00000495076.5	n.-74-3912G>A		intron_variant	Intron 1 of 18	5		ENSP00000434678.1
MICAL3	ENST00000672019.1	n.-74-3912G>A		intron_variant	Intron 1 of 32			ENSP00000500702.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28394 AN: 152066 Hom.: 2727 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.187 AC: 28403 AN: 152184 Hom.: 2727 Cov.: 32 AF XY: 0.190 AC XY: 14171 AN XY: 74420

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.198

Alfa AF: 0.177 Hom.: 4928

Bravo AF: 0.189

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.95
DANN	Benign	0.39

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: rs4819648; hg19: chr22-18393564;