Genetic Variant MSTO1:p.Ala5Val (chr1-155610262-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018116.4(MSTO1):c.14C>T(p.Ala5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 764,272 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0016 ( 2 hom. )

Consequence

MSTO1
NM_018116.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.60

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00959298).

BP6

Variant 1-155610262-C-T is Benign according to our data. Variant chr1-155610262-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2456933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00151 (228/151284) while in subpopulation NFE AF = 0.00185 (125/67750). AF 95% confidence interval is 0.00158. There are 0 homozygotes in GnomAd4. There are 100 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

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.14C>T	p.Ala5Val	missense	Exon 1 of 14	NP_060586.2
MSTO1	NM_001256532.1		c.14C>T	p.Ala5Val	missense	Exon 1 of 14	NP_001243461.1	Q9BUK6-2
MSTO1	NM_001350772.1		c.14C>T	p.Ala5Val	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.14C>T	p.Ala5Val	missense	Exon 1 of 14	ENSP00000245564.3	Q9BUK6-1
MSTO1	ENST00000368341.8	TSL:2	c.14C>T	p.Ala5Val	missense	Exon 1 of 13	ENSP00000357325.4	Q9BUK6-7
MSTO1	ENST00000490743.5	TSL:1	n.14C>T		non_coding_transcript_exon	Exon 1 of 13	ENSP00000476353.1	Q9BUK6-4

Frequencies

GnomAD3 genomes

AF:

0.00151

AC:

228

AN:

151170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000414

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.000526

Gnomad ASJ

AF:

0.0122

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00170

Gnomad FIN

AF:

0.0000953

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.000968

GnomAD2 exomes

AF:

0.00134

AC:

154

AN:

114550

AF XY:

0.00131

show subpopulations

Gnomad AFR exome

AF:

0.000503

Gnomad AMR exome

AF:

0.000433

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00190

Gnomad OTH exome

AF:

0.00171

GnomAD4 exome

AF:

0.00159

AC:

974

AN:

612988

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

503

AN XY:

317660

show subpopulations

African (AFR)

AF:

0.000694

AC:

AN:

15854

American (AMR)

AF:

0.000547

AC:

AN:

23762

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

154

AN:

14848

East Asian (EAS)

AF:

0.00

AC:

AN:

34108

South Asian (SAS)

AF:

0.000545

AC:

AN:

53202

European-Finnish (FIN)

AF:

0.0000869

AC:

AN:

34524

Middle Eastern (MID)

AF:

0.00178

AC:

AN:

2248

European-Non Finnish (NFE)

AF:

0.00174

AC:

701

AN:

402974

Other (OTH)

AF:

0.00187

AC:

AN:

31468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

102

153

204

255

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:

0.00151

AC:

228

AN:

151284

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

100

AN XY:

73878

show subpopulations

African (AFR)

AF:

0.000412

AC:

AN:

41224

American (AMR)

AF:

0.000526

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.0122

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00170

AC:

AN:

4710

European-Finnish (FIN)

AF:

0.0000953

AC:

AN:

10492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00185

AC:

125

AN:

67750

Other (OTH)

AF:

0.000958

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00135

Hom.:

Bravo

AF:

0.00168

ExAC

AF:

0.000974

AC:

106

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.71

M_CAP

Benign

0.0073

MetaRNN

Benign

0.0096

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.83

PhyloP100

1.6

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.97

REVEL

Benign

0.018

Sift

Benign

0.32

Sift4G

Benign

0.58

Polyphen

0.19

Vest4

0.20

MVP

0.31

MPC

1.8

ClinPred

0.0089

GERP RS

3.3

PromoterAI

0.064

Neutral

(source)

Varity_R

0.039

gMVP

0.32

Mutation Taster

=92/8

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over