Genetic Variant MIX23:p.Arg135Gln (chr3-122359900-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001017928.4(MIX23):c.404G>A(p.Arg135Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000286 in 1,505,378 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

MIX23
NM_001017928.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.64

Publications

0 publications found

Variant links:

Genes affected

MIX23 (HGNC:31136): (mitochondrial matrix import factor 23) Predicted to be located in mitochondrial intermembrane space. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

MIX23 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017928.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIX23	NM_001017928.4	MANE Select	c.404G>A	p.Arg135Gln	missense	Exon 5 of 5	NP_001017928.1	Q4VC31
	MIX23	NM_001308326.2		c.362G>A	p.Arg121Gln	missense	Exon 5 of 5	NP_001295255.1	C9JQ41

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIX23	ENST00000291458.9	TSL:1 MANE Select	c.404G>A	p.Arg135Gln	missense	Exon 5 of 5	ENSP00000291458.5	Q4VC31
MIX23	ENST00000906686.1		c.482G>A	p.Arg161Gln	missense	Exon 6 of 6	ENSP00000576745.1
MIX23	ENST00000479414.1	TSL:3	c.392G>A	p.Arg131Gln	missense	Exon 5 of 5	ENSP00000418810.1	H7C525

Frequencies

GnomAD3 genomes

AF:

0.0000139

AC:

AN:

143388

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000261

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:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

218630

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

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:

0.0000301

AC:

AN:

1361990

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

678090

show subpopulations

African (AFR)

AF:

0.0000359

AC:

AN:

27856

American (AMR)

AF:

0.00

AC:

AN:

34622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23844

East Asian (EAS)

AF:

0.00

AC:

AN:

31550

South Asian (SAS)

AF:

0.0000642

AC:

AN:

77874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5352

European-Non Finnish (NFE)

AF:

0.0000322

AC:

AN:

1056456

Other (OTH)

AF:

0.0000182

AC:

AN:

55044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.0000139

AC:

AN:

143388

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

69324

show subpopulations

African (AFR)

AF:

0.0000261

AC:

AN:

38252

American (AMR)

AF:

0.00

AC:

AN:

14134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3412

East Asian (EAS)

AF:

0.00

AC:

AN:

4718

South Asian (SAS)

AF:

0.00

AC:

AN:

4482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8652

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66596

Other (OTH)

AF:

0.00

AC:

AN:

1962

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

Alfa

AF:

0.00

Hom.:

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

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.083

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.57

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.8

PhyloP100

5.6

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.26

Sift

Benign

0.085

Sift4G

Benign

0.18

Polyphen

0.018

Vest4

0.56

MutPred

0.67

Loss of MoRF binding (P = 0.0097)

MVP

0.35

MPC

0.68

ClinPred

0.97

GERP RS

4.7

Varity_R

0.35

gMVP

0.87

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over