Genetic Variant MICU3:p.Pro42Arg (chr8-17027404-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_181723.3(MICU3):c.125C>G(p.Pro42Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,421,408 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

MICU3
NM_181723.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.070183545).

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>G	p.Pro42Arg	missense	Exon 1 of 15	NP_859074.1	Q86XE3
MICU3	NM_001349810.2		c.125C>G	p.Pro42Arg	missense	Exon 1 of 15	NP_001336739.1
MICU3	NM_001413217.1		c.125C>G	p.Pro42Arg	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>G	p.Pro42Arg	missense	Exon 1 of 15	ENSP00000321455.5	Q86XE3
MICU3	ENST00000952687.1		c.125C>G	p.Pro42Arg	missense	Exon 1 of 15	ENSP00000622746.1
MICU3	ENST00000952690.1		c.125C>G	p.Pro42Arg	missense	Exon 1 of 15	ENSP00000622749.1

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000474

AC:

AN:

84446

AF XY:

0.0000615

show subpopulations

Gnomad AFR exome

AF:

0.000736

Gnomad AMR exome

AF:

0.00

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:

0.00000709

AC:

AN:

1269362

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

623340

show subpopulations

African (AFR)

AF:

0.000351

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:

36978

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: 0.458

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

AF:

0.0000987

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.000362

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000166

ExAC

AF:

0.0000516

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

Benign

0.094

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0084

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

0.29

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.11

REVEL

Benign

0.026

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Polyphen

0.64

Vest4

0.38

MVP

0.20

MPC

0.90

ClinPred

0.032

GERP RS

1.1

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.078

gMVP

0.24

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over