rs1227564606

Variant names:

• chr7-1437547-T-C
• rs1227564606
• NM_182924.4:c.2464A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_182924.4(MICALL2):​c.2464A>G​(p.Met822Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000393 in 1,527,566 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: MICALL2 NM_182924.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07
• Publications: 0 publications found

Genes affected

MICALL2 (HGNC:29672): (MICAL like 2) Enables filamin binding activity. Involved in positive regulation of protein targeting to mitochondrion. Predicted to be located in several cellular components, including bicellular tight junction; neuron projection; and recycling endosome. Predicted to colocalize with stress fiber. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182924.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICALL2	NM_182924.4	MANE Select	c.2464A>G	p.Met822Val	missense	Exon 14 of 17	NP_891554.1	Q8IY33-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICALL2	ENST00000297508.8	TSL:1 MANE Select	c.2464A>G	p.Met822Val	missense	Exon 14 of 17	ENSP00000297508.7	Q8IY33-1
	MICALL2	ENST00000873416.1		c.2449A>G	p.Met817Val	missense	Exon 14 of 17	ENSP00000543475.1
	MICALL2	ENST00000873414.1		c.2440A>G	p.Met814Val	missense	Exon 14 of 17	ENSP00000543473.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151398 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000291 AC: 4 AN: 1376168 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 679356

African (AFR) AF: 0.00 AC: 0 AN: 30348

American (AMR) AF: 0.00 AC: 0 AN: 33142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24772

East Asian (EAS) AF: 0.00 AC: 0 AN: 35434

South Asian (SAS) AF: 0.00 AC: 0 AN: 78398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4446

European-Non Finnish (NFE) AF: 0.00000372 AC: 4 AN: 1075922

Other (OTH) AF: 0.00 AC: 0 AN: 57322

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151398 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 73988

African (AFR) AF: 0.0000246 AC: 1 AN: 40672

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.1
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.059
Sift	Benign	0.039	D
Sift4G	Benign	0.13	T
Polyphen		0.94	P
Vest4		0.56
MutPred		0.40		Loss of helix (P = 0.0017)
MVP		0.32
MPC		0.040
ClinPred		0.69	D
GERP RS		2.1
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Varity_R		0.31
gMVP		0.36
Mutation Taster		=78/22	polymorphism

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: rs1227564606; hg19: chr7-1477183;