Genetic Variant MICALL2:p.Glu837Asp (chr7-1436822-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_182924.4(MICALL2):c.2511G>C(p.Glu837Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000551 in 1,452,290 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MICALL2
NM_182924.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.268

Publications

0 publications found

Variant links:

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]

MICALL2 links:

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ACMG classification

Classification was made for transcript

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.2511G>C	p.Glu837Asp	missense	Exon 15 of 17	NP_891554.1	Q8IY33-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MICALL2	ENST00000297508.8	TSL:1 MANE Select	c.2511G>C	p.Glu837Asp	missense	Exon 15 of 17	ENSP00000297508.7	Q8IY33-1
MICALL2	ENST00000873416.1		c.2496G>C	p.Glu832Asp	missense	Exon 15 of 17	ENSP00000543475.1
MICALL2	ENST00000873414.1		c.2487G>C	p.Glu829Asp	missense	Exon 15 of 17	ENSP00000543473.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000342

AC:

AN:

234146

AF XY:

0.0000233

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000241

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000551

AC:

AN:

1452290

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722480

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32974

American (AMR)

AF:

0.000181

AC:

AN:

44172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25960

East Asian (EAS)

AF:

0.00

AC:

AN:

38902

South Asian (SAS)

AF:

0.00

AC:

AN:

85634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49784

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109148

Other (OTH)

AF:

0.00

AC:

AN:

59966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000249

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.00081

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.70

MetaSVM

Uncertain

-0.22

MutationAssessor

Pathogenic

3.3

PhyloP100

-0.27

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.26

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.71

MutPred

0.32

Gain of helix (P = 0.0496)

MVP

0.76

MPC

0.077

ClinPred

0.83

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.59

Mutation Taster

=71/29

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over