Genetic Variant MICU3:p.Pro42His (chr8-17027404-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_181723.3(MICU3):c.125C>A(p.Pro42His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000788 in 1,269,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. P42R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

MICU3
NM_181723.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.294

Publications

0 publications found

Variant links:

Genes affected

MICU3 (HGNC:27820): (mitochondrial calcium uptake family member 3) Predicted to enable calcium ion binding activity. Predicted to be involved in calcium import into the mitochondrion and mitochondrial calcium ion homeostasis. Predicted to be located in mitochondrial inner membrane. Predicted to be part of uniplex complex. [provided by Alliance of Genome Resources, Apr 2022]

MICU3 links:

ENSG00000289225 (HGNC:):

ENSG00000289225 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28890502).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181723.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MICU3	NM_181723.3	MANE Select	c.125C>A	p.Pro42His	missense	Exon 1 of 15	NP_859074.1	Q86XE3
MICU3	NM_001349810.2		c.125C>A	p.Pro42His	missense	Exon 1 of 15	NP_001336739.1
MICU3	NM_001413217.1		c.125C>A	p.Pro42His	missense	Exon 1 of 14	NP_001400146.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MICU3	ENST00000318063.10	TSL:1 MANE Select	c.125C>A	p.Pro42His	missense	Exon 1 of 15	ENSP00000321455.5	Q86XE3
MICU3	ENST00000952687.1		c.125C>A	p.Pro42His	missense	Exon 1 of 15	ENSP00000622746.1
MICU3	ENST00000952690.1		c.125C>A	p.Pro42His	missense	Exon 1 of 15	ENSP00000622749.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.88e-7

AC:

AN:

1269360

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

623340

show subpopulations

African (AFR)

AF:

0.0000390

AC:

AN:

25620

American (AMR)

AF:

0.00

AC:

AN:

18962

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17902

East Asian (EAS)

AF:

0.00

AC:

AN:

30978

South Asian (SAS)

AF:

0.00

AC:

AN:

55474

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36976

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4208

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1027664

Other (OTH)

AF:

0.00

AC:

AN:

51576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0078

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.29

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.24

REVEL

Benign

0.081

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

0.95

Vest4

0.42

MutPred

0.14

Loss of glycosylation at P42 (P = 0.0513)

MVP

0.25

MPC

0.95

ClinPred

0.17

GERP RS

1.1

PromoterAI

-0.014

Neutral

(source)

Varity_R

0.18

gMVP

0.22

Mutation Taster

=93/7

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