Genetic Variant MSTO1:p.Gln12* (chr1-155610282-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_018116.4(MSTO1):c.34C>T(p.Gln12*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MSTO1
NM_018116.4 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.43

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: Likely_pathogenic. The variant received 6 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 17 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

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.34C>T	p.Gln12*	stop_gained	Exon 1 of 14	NP_060586.2
MSTO1	NM_001256532.1		c.34C>T	p.Gln12*	stop_gained	Exon 1 of 14	NP_001243461.1	Q9BUK6-2
MSTO1	NM_001350772.1		c.34C>T	p.Gln12*	stop_gained	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.34C>T	p.Gln12*	stop_gained	Exon 1 of 14	ENSP00000245564.3	Q9BUK6-1
MSTO1	ENST00000368341.8	TSL:2	c.34C>T	p.Gln12*	stop_gained	Exon 1 of 13	ENSP00000357325.4	Q9BUK6-7
MSTO1	ENST00000490743.5	TSL:1	n.34C>T		non_coding_transcript_exon	Exon 1 of 13	ENSP00000476353.1	Q9BUK6-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

832482

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

421304

African (AFR)

AF:

0.00

AC:

AN:

19868

American (AMR)

AF:

0.00

AC:

AN:

25824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16256

East Asian (EAS)

AF:

0.00

AC:

AN:

35578

South Asian (SAS)

AF:

0.00

AC:

AN:

58274

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2664

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

599942

Other (OTH)

AF:

0.00

AC:

AN:

38680

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.53

BayesDel_noAF

Pathogenic

0.52

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.80

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.87

PhyloP100

5.4

Vest4

0.22

GERP RS

3.3

PromoterAI

0.033

Neutral

(source)

Mutation Taster

=9/191

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over