Genetic Variant MSTO1:p.Pro41Thr (chr1-155610461-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018116.4(MSTO1):c.121C>A(p.Pro41Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 65 hom., cov: 18)

Exomes 𝑓: 0.0024 ( 48 hom. )

Failed GnomAD Quality Control

Consequence

MSTO1
NM_018116.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.406

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 links:

LOC105371452 (HGNC:):

LOC105371452 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017667115).

BP6

Variant 1-155610461-C-A is Benign according to our data. Variant chr1-155610461-C-A is described in ClinVar as [Benign]. Clinvar id is 1288287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSTO1	NM_018116.4 link	c.121C>A	p.Pro41Thr	missense_variant	Exon 2 of 14	ENST00000245564.8	NP_060586.2	Q9BUK6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSTO1	ENST00000245564.8 link	c.121C>A	p.Pro41Thr	missense_variant	Exon 2 of 14	1	NM_018116.4	ENSP00000245564.3		Q9BUK6-1
MSTO1	ENST00000368341.8 link	c.121C>A	p.Pro41Thr	missense_variant	Exon 2 of 13	2		ENSP00000357325.4		Q9BUK6-7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

2192

AN:

130756

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0630

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00424

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000453

Gnomad SAS

AF:

0.000591

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00658

Gnomad NFE

AF:

0.000227

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00575

AC:

479

AN:

83238

Hom.:

AF XY:

0.00448

AC XY:

193

AN XY:

43048

show subpopulations

Gnomad AFR exome

AF:

0.0691

Gnomad AMR exome

AF:

0.00284

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000210

Gnomad SAS exome

AF:

0.000339

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.00238

AC:

1627

AN:

684694

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

699

AN XY:

354844

show subpopulations

Gnomad4 AFR exome

AF:

0.0688

Gnomad4 AMR exome

AF:

0.00353

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000122

Gnomad4 SAS exome

AF:

0.000540

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000944

Gnomad4 OTH exome

AF:

0.00518

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0168

AC:

2193

AN:

130864

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

985

AN XY:

62480

show subpopulations

Gnomad4 AFR

AF:

0.0628

Gnomad4 AMR

AF:

0.00423

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000454

Gnomad4 SAS

AF:

0.000296

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000227

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00108

Hom.:

ExAC

AF:

0.00183

AC:

165

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.7

DANN

Benign

0.81

DEOGEN2

Benign

0.0076

.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.74

T;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

.;L;L

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.9

.;N;N

REVEL

Benign

0.079

Sift

Benign

0.086

.;T;T

Sift4G

Benign

0.72

.;T;T

Polyphen

0.83

.;P;.

Vest4

0.11, 0.13

MVP

0.14

MPC

2.1

ClinPred

0.029

GERP RS

-1.5

Varity_R

0.039

gMVP

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over