Genetic Variant MICALL2:p.Val855Met (chr7-1436770-C-T) – 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.2563G>A(p.Val855Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,455,590 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V855L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MICALL2
NM_182924.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.835

Publications

2 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:

Genome browser will be placed here

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.2563G>A	p.Val855Met	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.2563G>A	p.Val855Met	missense	Exon 15 of 17	ENSP00000297508.7	Q8IY33-1
MICALL2	ENST00000873416.1		c.2548G>A	p.Val850Met	missense	Exon 15 of 17	ENSP00000543475.1
MICALL2	ENST00000873414.1		c.2539G>A	p.Val847Met	missense	Exon 15 of 17	ENSP00000543473.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000832

AC:

AN:

240296

AF XY:

0.00000763

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000486

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1455590

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33144

American (AMR)

AF:

0.00

AC:

AN:

44362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26012

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39252

South Asian (SAS)

AF:

0.0000349

AC:

AN:

85852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50818

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110220

Other (OTH)

AF:

0.00

AC:

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.00000378

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.32

MutationAssessor

Pathogenic

3.5

PhyloP100

0.83

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.3

REVEL

Benign

0.26

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.48

MVP

0.61

MPC

0.073

ClinPred

0.73

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.49

Mutation Taster

=74/26

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