Variant 1-155610565-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_018116.4(MSTO1):c.220+5G>C variant causes a splice donor 5th base, intron change. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000076 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MSTO1
NM_018116.4 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.9992

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 3.75

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 Uncertain_significance. Variant got 1 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSTO1	NM_018116.4 linkuse as main transcript	c.220+5G>C		splice_donor_5th_base_variant, intron_variant		ENST00000245564.8
LOC105371452	XR_922171.2 linkuse as main transcript	n.77-673C>G		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.220+5G>C		splice_donor_5th_base_variant, intron_variant		1	NM_018116.4	P1	Q9BUK6-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

143732

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000694

Gnomad ASJ

AF:

0.00178

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000152

Gnomad OTH

AF:

0.000513

GnomAD3 exomes

AF:

0.0000325

AC:

AN:

61574

Hom.:

AF XY:

0.0000323

AC XY:

AN XY:

30986

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00127

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000761

AC:

AN:

749220

Hom.:

Cov.:

AF XY:

0.0000680

AC XY:

AN XY:

382472

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00253

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000626

AC:

AN:

143732

Hom.:

Cov.:

AF XY:

0.0000720

AC XY:

AN XY:

69484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000694

Gnomad4 ASJ

AF:

0.00178

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000152

Gnomad4 OTH

AF:

0.000513

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

See cases

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Laboratory of Genetics in Ophthalmology, Institut Imagine

Jun 17, 2022

The c.220+5 variant in MSTO1 has been identified in compound heterozygosity with a likely pathogenic missense change (c.65A>G, p.Ala22Glu) in three siblings affected with typical MSTO1-assciated myoptahy, cerbellar atrophy and corticospinal track involvement and previously unreported bilateral optic neuropathy responsible for profound central visual loss. Biallelism has been demonstrated experimentaly. The change is known as rs1187504822 and is extremely rare with a minor allele frequency of 0.003%. The variant is predicted to abolish the donor splice-site of intron 2, induce exon skipping and introduce a premature termination codon in the mRNA. The mRNA encoded by the allele carrying the c.200+5G>C variant is undetectable in cells from affected individuals, suggesting nonsense-mediated mRNA decay. In summary, the c.220+5G>C variant meets our criteria to be classified as pathogenic based upon phenotype, family history, segregation studies, rarity in large population studies, computational evidence supporting deleterious effect and mRNA analysis. -

Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

May 31, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.59

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.59

Position offset: -5

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