rs11917

Variant names:

• chr22-17860245-C-A
• rs11917
• NM_015241.3:c.2605+4654G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015241.3(MICAL3):​c.2605+4654G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 984,648 control chromosomes in the GnomAD database, including 81,118 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 0.48 (18865 hom., cov: 33)
  • Exomes 𝑓: 0.38 (62253 hom.)
• Consequence: MICAL3 NM_015241.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICAL3	NM_015241.3	c.2605+4654G>T		intron_variant	Intron 19 of 31	ENST00000441493.7	NP_056056.2
MICAL3	NM_001136004.3	c.*4409G>T		3_prime_UTR_variant	Exon 22 of 22		NP_001129476.1
MICAL3	NM_001122731.2	c.2605+4654G>T		intron_variant	Intron 18 of 19		NP_001116203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICAL3	ENST00000441493.7	c.2605+4654G>T		intron_variant	Intron 19 of 31	5	NM_015241.3	ENSP00000416015.2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73315 AN: 151934 Hom.: 18808 Cov.: 33

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.466

GnomAD4 exome AF: 0.383 AC: 319137 AN: 832596 Hom.: 62253 Cov.: 26 AF XY: 0.383 AC XY: 147368 AN XY: 384520

African (AFR) AF: 0.700 AC: 11040 AN: 15770

American (AMR) AF: 0.565 AC: 555 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 2304 AN: 5148

East Asian (EAS) AF: 0.508 AC: 1842 AN: 3626

South Asian (SAS) AF: 0.345 AC: 5672 AN: 16448

European-Finnish (FIN) AF: 0.371 AC: 103 AN: 278

Middle Eastern (MID) AF: 0.439 AC: 711 AN: 1620

European-Non Finnish (NFE) AF: 0.375 AC: 285722 AN: 761448

Other (OTH) AF: 0.410 AC: 11188 AN: 27276

GnomAD4 genome AF: 0.483 AC: 73439 AN: 152052 Hom.: 18865 Cov.: 33 AF XY: 0.485 AC XY: 36019 AN XY: 74326

African (AFR) AF: 0.670 AC: 27780 AN: 41446

American (AMR) AF: 0.525 AC: 8014 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1500 AN: 3464

East Asian (EAS) AF: 0.489 AC: 2533 AN: 5184

South Asian (SAS) AF: 0.373 AC: 1800 AN: 4822

European-Finnish (FIN) AF: 0.418 AC: 4414 AN: 10572

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.380 AC: 25845 AN: 67980

Other (OTH) AF: 0.467 AC: 989 AN: 2116

Alfa AF: 0.378 Hom.: 2096

Bravo AF: 0.504

Asia WGS AF: 0.462 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	6.0
DANN	Benign	0.83
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11917; hg19: chr22-18343011;