Genetic Variant NM_018116.4:c.34C>G (chr1-155610282-C-G) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_018116.4(MSTO1):c.34C>G(p.Gln12Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000012 in 832,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

MSTO1
NM_018116.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.43

Publications

0 publications found

Variant links:

Genes affected

MSTO1 (HGNC:29678): (misato mitochondrial distribution and morphology regulator 1) Involved in mitochondrion distribution. Located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

MSTO1 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Broad Center for Mendelian Genomics, Ambry Genetics

MSTO1 links:

ENSG00000232519 (HGNC:):

ENSG00000232519 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.941

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018116.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSTO1	NM_018116.4	MANE Select	c.34C>G	p.Gln12Glu	missense	Exon 1 of 14	NP_060586.2
MSTO1	NM_001256532.1		c.34C>G	p.Gln12Glu	missense	Exon 1 of 14	NP_001243461.1	Q9BUK6-2
MSTO1	NM_001350772.1		c.34C>G	p.Gln12Glu	missense	Exon 1 of 14	NP_001337701.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSTO1	ENST00000245564.8	TSL:1 MANE Select	c.34C>G	p.Gln12Glu	missense	Exon 1 of 14	ENSP00000245564.3	Q9BUK6-1
MSTO1	ENST00000368341.8	TSL:2	c.34C>G	p.Gln12Glu	missense	Exon 1 of 13	ENSP00000357325.4	Q9BUK6-7
MSTO1	ENST00000490743.5	TSL:1	n.34C>G		non_coding_transcript_exon	Exon 1 of 13	ENSP00000476353.1	Q9BUK6-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000120

AC:

AN:

832482

Hom.:

Cov.:

AF XY:

0.00000237

AC XY:

AN XY:

421304

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19868

American (AMR)

AF:

0.00

AC:

AN:

25824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16256

East Asian (EAS)

AF:

0.00

AC:

AN:

35578

South Asian (SAS)

AF:

0.00

AC:

AN:

58274

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2664

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

599942

Other (OTH)

AF:

0.0000259

AC:

AN:

38680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.034

MetaRNN

Pathogenic

0.94

MetaSVM

Uncertain

0.23

MutationAssessor

Pathogenic

3.3

PhyloP100

5.4

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-2.5

REVEL

Pathogenic

0.70

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.84

MutPred

0.85

Gain of loop (P = 0.1069)

MVP

0.80

MPC

3.5

ClinPred

0.99

GERP RS

3.3

PromoterAI

0.050

Neutral

(source)

Varity_R

0.66

gMVP

0.85

Mutation Taster

=61/39

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over