Genetic Variant MICU3:p.Glu49Gly (chr8-17027425-A-G) – 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.146A>G(p.Glu49Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MICU3
NM_181723.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.963

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:

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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=0.08334851).

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.146A>G	p.Glu49Gly	missense	Exon 1 of 15	NP_859074.1	Q86XE3
MICU3	NM_001349810.2		c.146A>G	p.Glu49Gly	missense	Exon 1 of 15	NP_001336739.1
MICU3	NM_001413217.1		c.146A>G	p.Glu49Gly	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.146A>G	p.Glu49Gly	missense	Exon 1 of 15	ENSP00000321455.5	Q86XE3
MICU3	ENST00000952687.1		c.146A>G	p.Glu49Gly	missense	Exon 1 of 15	ENSP00000622746.1
MICU3	ENST00000952690.1		c.146A>G	p.Glu49Gly	missense	Exon 1 of 15	ENSP00000622749.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1197240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

580748

African (AFR)

AF:

0.00

AC:

AN:

24194

American (AMR)

AF:

0.00

AC:

AN:

12926

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16332

East Asian (EAS)

AF:

0.00

AC:

AN:

28464

South Asian (SAS)

AF:

0.00

AC:

AN:

43428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32796

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3546

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

987080

Other (OTH)

AF:

0.00

AC:

AN:

48474

GnomAD4 genome

Cov.:

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

0.081

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0088

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.56

M_CAP

Benign

0.066

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.96

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.28

REVEL

Benign

0.024

Sift

Benign

0.036

Sift4G

Benign

0.16

Polyphen

0.0

Vest4

0.27

MutPred

0.23

Gain of MoRF binding (P = 0.0337)

MVP

0.14

MPC

0.98

ClinPred

0.58

GERP RS

1.9

PromoterAI

-0.027

Neutral

(source)

Varity_R

0.088

gMVP

0.21

Mutation Taster

=88/12

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over