Genetic Variant MSTO1:c.-260C>T (chr1-155609989-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_StrongBA1

The ENST00000697770.1(MSTO1):c.-378-1050C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00657 in 501,810 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 90 hom., cov: 29)

Exomes 𝑓: 0.0017 ( 17 hom. )

Consequence

MSTO1
ENST00000697770.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.11

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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-155609989-C-T is Benign according to our data. Variant chr1-155609989-C-T is described in ClinVar as Benign. ClinVar VariationId is 1260671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000697770.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MSTO1	NM_018116.4	MANE Select	c.-260C>T	upstream_gene	N/A	NP_060586.2
MSTO1	NM_001256532.1		c.-260C>T	upstream_gene	N/A	NP_001243461.1	Q9BUK6-2
MSTO1	NM_001350772.1		c.-260C>T	upstream_gene	N/A	NP_001337701.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MSTO1	ENST00000697770.1		c.-378-1050C>T	intron	N/A	ENSP00000513434.1	A0A8V8TLP0
ENSG00000232519	ENST00000456382.2	TSL:5	n.104-97G>A	intron	N/A
MSTO1	ENST00000245564.8	TSL:1 MANE Select	c.-260C>T	upstream_gene	N/A	ENSP00000245564.3	Q9BUK6-1

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2684

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0624

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0129

GnomAD4 exome

AF:

0.00174

AC:

609

AN:

349504

Hom.:

AF XY:

0.00150

AC XY:

275

AN XY:

183220

show subpopulations

African (AFR)

AF:

0.0567

AC:

456

AN:

8048

American (AMR)

AF:

0.00272

AC:

AN:

10658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10740

East Asian (EAS)

AF:

0.00

AC:

AN:

22998

South Asian (SAS)

AF:

0.000265

AC:

AN:

34008

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1594

European-Non Finnish (NFE)

AF:

0.000175

AC:

AN:

216530

Other (OTH)

AF:

0.00371

AC:

AN:

20774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

120

150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0176

AC:

2687

AN:

152306

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1282

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0623

AC:

2587

AN:

41534

American (AMR)

AF:

0.00372

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68024

Other (OTH)

AF:

0.0128

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

127

253

380

506

633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00162

Hom.:

Bravo

AF:

0.0196

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.30

(source)

DANN

Benign

0.79

PhyloP100

-3.1

PromoterAI

-0.014

Neutral

(source)

Splicing

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