Genetic Variant MSTO1:p.His15Arg (chr1-155610292-A-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_018116.4(MSTO1):c.44A>G(p.His15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000107 in 930,416 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: 0.0000011 ( 0 hom. )

Consequence

MSTO1
NM_018116.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.786

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.44A>G	p.His15Arg	missense	Exon 1 of 14	NP_060586.2
MSTO1	NM_001256532.1		c.44A>G	p.His15Arg	missense	Exon 1 of 14	NP_001243461.1	Q9BUK6-2
MSTO1	NM_001350772.1		c.44A>G	p.His15Arg	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.44A>G	p.His15Arg	missense	Exon 1 of 14	ENSP00000245564.3	Q9BUK6-1
MSTO1	ENST00000368341.8	TSL:2	c.44A>G	p.His15Arg	missense	Exon 1 of 13	ENSP00000357325.4	Q9BUK6-7
MSTO1	ENST00000490743.5	TSL:1	n.44A>G		non_coding_transcript_exon	Exon 1 of 13	ENSP00000476353.1	Q9BUK6-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000107

AC:

AN:

930416

Hom.:

Cov.:

AF XY:

0.00000214

AC XY:

AN XY:

466774

show subpopulations

African (AFR)

AF:

0.0000462

AC:

AN:

21630

American (AMR)

AF:

0.00

AC:

AN:

26092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16888

East Asian (EAS)

AF:

0.00

AC:

AN:

36048

South Asian (SAS)

AF:

0.00

AC:

AN:

60228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35546

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2850

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

689366

Other (OTH)

AF:

0.00

AC:

AN:

41768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000416

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

Uncertain

0.54

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.060

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.65

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.79

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

PhyloP100

1.5

PrimateAI

Pathogenic

0.93

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.48

Sift

Uncertain

0.019

Sift4G

Uncertain

0.037

Polyphen

0.88

Vest4

0.66

MutPred

0.76

Gain of MoRF binding (P = 0.0146)

MVP

0.69

MPC

3.9

ClinPred

0.92

GERP RS

3.3

PromoterAI

-0.051

Neutral

(source)

Varity_R

0.35

gMVP

0.72

Mutation Taster

=71/29

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