Genetic Variant NM_181723.3:c.370G>T (chr8-17027649-G-T) – 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.370G>T(p.Ala124Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. A124T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MICU3
NM_181723.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.35

Publications

1 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:

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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=0.2689971).

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.370G>T	p.Ala124Ser	missense	Exon 1 of 15	NP_859074.1	Q86XE3
MICU3	NM_001349810.2		c.370G>T	p.Ala124Ser	missense	Exon 1 of 15	NP_001336739.1
MICU3	NM_001413217.1		c.370G>T	p.Ala124Ser	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.370G>T	p.Ala124Ser	missense	Exon 1 of 15	ENSP00000321455.5	Q86XE3
MICU3	ENST00000952687.1		c.370G>T	p.Ala124Ser	missense	Exon 1 of 15	ENSP00000622746.1
MICU3	ENST00000952690.1		c.370G>T	p.Ala124Ser	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:

1148662

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

552336

African (AFR)

AF:

0.00

AC:

AN:

23374

American (AMR)

AF:

0.00

AC:

AN:

9402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15742

East Asian (EAS)

AF:

0.00

AC:

AN:

26948

South Asian (SAS)

AF:

0.00

AC:

AN:

37816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25880

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3132

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

959896

Other (OTH)

AF:

0.00

AC:

AN:

46472

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

PhyloP100

4.4

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.37

REVEL

Benign

0.10

Sift

Benign

0.23

Sift4G

Benign

0.71

Polyphen

0.99

Vest4

0.42

MutPred

0.23

Gain of glycosylation at A124 (P = 0.0251)

MVP

0.38

MPC

0.81

ClinPred

0.73

GERP RS

3.2

PromoterAI

-0.015

Neutral

(source)

Varity_R

0.091

gMVP

0.40

Mutation Taster

=81/19

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