dbSNP rs412421: MSTO1:c.-209C>T (chr1-155610040-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000697770.1(MSTO1):c.-378-999C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0065 in 591,354 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 102 hom., cov: 28)

Exomes 𝑓: 0.0017 ( 23 hom. )

Consequence

MSTO1
ENST00000697770.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.145

Publications

1 publications found

Variant links:

COSMIC-nc: COSV99824065

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 1-155610040-C-T is Benign according to our data. Variant chr1-155610040-C-T is described in ClinVar as Benign. ClinVar VariationId is 1287807.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0689 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.-209C>T	upstream_gene	N/A	NP_060586.2
MSTO1	NM_001256532.1		c.-209C>T	upstream_gene	N/A	NP_001243461.1	Q9BUK6-2
MSTO1	NM_001350772.1		c.-209C>T	upstream_gene	N/A	NP_001337701.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MSTO1	ENST00000697770.1		c.-378-999C>T	intron	N/A	ENSP00000513434.1	A0A8V8TLP0
ENSG00000232519	ENST00000456382.2	TSL:5	n.104-148G>A	intron	N/A
MSTO1	ENST00000245564.8	TSL:1 MANE Select	c.-209C>T	upstream_gene	N/A	ENSP00000245564.3	Q9BUK6-1

Frequencies

GnomAD3 genomes

AF:

0.0203

AC:

3086

AN:

151978

Hom.:

102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0712

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00544

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000832

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0149

GnomAD4 exome

AF:

0.00173

AC:

759

AN:

439258

Hom.:

AF XY:

0.00139

AC XY:

320

AN XY:

229648

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0494

AC:

543

AN:

11002

American (AMR)

AF:

0.00379

AC:

AN:

15320

Ashkenazi Jewish (ASJ)

AF:

0.0000771

AC:

AN:

12966

East Asian (EAS)

AF:

0.000106

AC:

AN:

28262

South Asian (SAS)

AF:

0.000370

AC:

AN:

43268

European-Finnish (FIN)

AF:

0.0000351

AC:

AN:

28514

Middle Eastern (MID)

AF:

0.00158

AC:

AN:

1898

European-Non Finnish (NFE)

AF:

0.000125

AC:

AN:

272974

Other (OTH)

AF:

0.00399

AC:

100

AN:

25054

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.378

Heterozygous variant carriers

126

158

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:

0.0203

AC:

3087

AN:

152096

Hom.:

102

Cov.:

AF XY:

0.0189

AC XY:

1407

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0711

AC:

2945

AN:

41442

American (AMR)

AF:

0.00543

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.000624

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

67986

Other (OTH)

AF:

0.0147

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

138

277

415

554

692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00155

Hom.:

Bravo

AF:

0.0231

ClinVar

ClinVar submissions

Significance:Benign

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

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.7

(source)

DANN

Benign

0.97

PhyloP100

0.14

PromoterAI

-0.11

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