dbSNP rs776637688: MICU3:p.Pro12Leu (chr8-17027314-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181723.3(MICU3):c.35C>T(p.Pro12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,507,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MICU3
NM_181723.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10230315).

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.35C>T	p.Pro12Leu	missense	Exon 1 of 15	NP_859074.1	Q86XE3
MICU3	NM_001349810.2		c.35C>T	p.Pro12Leu	missense	Exon 1 of 15	NP_001336739.1
MICU3	NM_001413217.1		c.35C>T	p.Pro12Leu	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.35C>T	p.Pro12Leu	missense	Exon 1 of 15	ENSP00000321455.5	Q86XE3
MICU3	ENST00000952687.1		c.35C>T	p.Pro12Leu	missense	Exon 1 of 15	ENSP00000622746.1
MICU3	ENST00000952690.1		c.35C>T	p.Pro12Leu	missense	Exon 1 of 15	ENSP00000622749.1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150342

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000182

AC:

AN:

164906

AF XY:

0.0000106

show subpopulations

Gnomad AFR exome

AF:

0.000120

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:

0.0000263

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1356910

Hom.:

Cov.:

AF XY:

0.0000148

AC XY:

AN XY:

674832

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27638

American (AMR)

AF:

0.00

AC:

AN:

34642

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22684

East Asian (EAS)

AF:

0.00

AC:

AN:

29814

South Asian (SAS)

AF:

0.00

AC:

AN:

78314

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5270

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

1067414

Other (OTH)

AF:

0.00

AC:

AN:

55310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.0000133

AC:

AN:

150342

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73296

show subpopulations

African (AFR)

AF:

0.0000244

AC:

AN:

40998

American (AMR)

AF:

0.00

AC:

AN:

15076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

4916

South Asian (SAS)

AF:

0.00

AC:

AN:

4736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10280

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67590

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.0000540

Hom.:

ExAC

AF:

0.0000169

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

0.14

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

1.2

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.49

REVEL

Benign

0.093

Sift

Pathogenic

0.0

Sift4G

Benign

0.18

Polyphen

0.0050

Vest4

0.32

MutPred

0.26

Loss of relative solvent accessibility (P = 0.008)

MVP

0.12

MPC

1.9

ClinPred

0.22

GERP RS

2.4

PromoterAI

0.066

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.15

gMVP

0.31

Mutation Taster

=98/2

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