Variant 1-155611218-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_018116.4(MSTO1):c.293A>G(p.Gln98Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000357 in 1,605,292 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

MSTO1
NM_018116.4 missense, splice_region

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 2.88

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0104598105).

BP6

Variant 1-155611218-A-G is Benign according to our data. Variant chr1-155611218-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 711292.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0018 (263/145838) while in subpopulation AFR AF= 0.00636 (254/39948). AF 95% confidence interval is 0.00572. There are 0 homozygotes in gnomad4. There are 123 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSTO1	NM_018116.4 linkuse as main transcript	c.293A>G	p.Gln98Arg	missense_variant, splice_region_variant	4/14	ENST00000245564.8
LOC105371452	XR_922171.2 linkuse as main transcript	n.77-1326T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSTO1	ENST00000245564.8 linkuse as main transcript	c.293A>G	p.Gln98Arg	missense_variant, splice_region_variant	4/14	1	NM_018116.4	P1	Q9BUK6-1

Frequencies

GnomAD3 genomes

AF:

0.00180

AC:

262

AN:

145724

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00635

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000302

Gnomad OTH

AF:

0.00155

GnomAD3 exomes

AF:

0.000474

AC:

110

AN:

232256

Hom.:

AF XY:

0.000348

AC XY:

AN XY:

126462

show subpopulations

Gnomad AFR exome

AF:

0.00682

Gnomad AMR exome

AF:

0.000160

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000353

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000287

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.000212

AC:

310

AN:

1459454

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

135

AN XY:

726024

show subpopulations

Gnomad4 AFR exome

AF:

0.00731

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000680

GnomAD4 genome

AF:

0.00180

AC:

263

AN:

145838

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

123

AN XY:

70690

show subpopulations

Gnomad4 AFR

AF:

0.00636

Gnomad4 AMR

AF:

0.000280

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000302

Gnomad4 OTH

AF:

0.00153

Alfa

AF:

0.000807

Hom.:

ESP6500AA

AF:

0.00413

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000536

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	MSTO1: PP2, BP4 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Uncertain

0.98

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.56

T;T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.43

Polyphen

0.010

.;B;.

Vest4

0.25, 0.39

MVP

0.16

MPC

2.0

ClinPred

0.0055

GERP RS

3.1

Varity_R

0.15

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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