Genetic Variant NM_018116.4:c.194C>T (chr1-155610534-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_018116.4(MSTO1):c.194C>T(p.Pro65Leu) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., cov: 18)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MSTO1
NM_018116.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.42

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:

LOC105371452 (HGNC:):

LOC105371452 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.978

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
MSTO1	NM_018116.4	MANE Select	c.194C>T	p.Pro65Leu	missense	Exon 2 of 14	NP_060586.2
MSTO1	NM_001350776.1		c.-94C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	NP_001337705.1
MSTO1	NM_001350777.1		c.-363C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	NP_001337706.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSTO1	ENST00000245564.8	TSL:1 MANE Select	c.194C>T	p.Pro65Leu	missense	Exon 2 of 14	ENSP00000245564.3	Q9BUK6-1
MSTO1	ENST00000368341.8	TSL:2	c.194C>T	p.Pro65Leu	missense	Exon 2 of 13	ENSP00000357325.4	Q9BUK6-7
MSTO1	ENST00000490743.5	TSL:1	n.194C>T		non_coding_transcript_exon	Exon 2 of 13	ENSP00000476353.1	Q9BUK6-4

Frequencies

GnomAD3 genomes

AF:

0.0000225

AC:

AN:

133402

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000289

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:

0.0000320

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

61518

AF XY:

0.00

show subpopulations

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:

0.0000414

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000471

AC:

AN:

848774

Hom.:

Cov.:

AF XY:

0.00000233

AC XY:

AN XY:

429928

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20472

American (AMR)

AF:

0.00

AC:

AN:

27336

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16688

East Asian (EAS)

AF:

0.00

AC:

AN:

34944

South Asian (SAS)

AF:

0.00

AC:

AN:

57624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2738

European-Non Finnish (NFE)

AF:

0.00000648

AC:

AN:

617386

Other (OTH)

AF:

0.00

AC:

AN:

39724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000225

AC:

AN:

133402

Hom.:

Cov.:

AF XY:

0.0000157

AC XY:

AN XY:

63632

show subpopulations

African (AFR)

AF:

0.0000289

AC:

AN:

34580

American (AMR)

AF:

0.00

AC:

AN:

13378

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3242

East Asian (EAS)

AF:

0.00

AC:

AN:

4588

South Asian (SAS)

AF:

0.00

AC:

AN:

3738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000320

AC:

AN:

62494

Other (OTH)

AF:

0.00

AC:

AN:

1794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.98

MetaSVM

Uncertain

0.71

MutationAssessor

Pathogenic

3.3

PhyloP100

5.4

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-8.7

REVEL

Pathogenic

0.82

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.79

MutPred

0.91

Loss of phosphorylation at T64 (P = 0.058)

MVP

0.97

MPC

3.4

ClinPred

0.99

GERP RS

3.2

PromoterAI

-0.014

Neutral

(source)

Varity_R

0.76

gMVP

0.83

Mutation Taster

=54/46

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over