chr1-155610249-A-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_018116.4(MSTO1):c.1A>C(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.0000264 in 151,766 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 28)
Consequence
MSTO1
NM_018116.4 start_lost
NM_018116.4 start_lost
Scores
2
5
4
Clinical Significance
Conservation
PhyloP100: 3.73
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-155610249-A-C is Pathogenic according to our data. Variant chr1-155610249-A-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2229213.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSTO1 | NM_018116.4 | c.1A>C | p.Met1? | start_lost | 1/14 | ENST00000245564.8 | |
LOC105371452 | XR_922171.2 | n.77-357T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSTO1 | ENST00000245564.8 | c.1A>C | p.Met1? | start_lost | 1/14 | 1 | NM_018116.4 | P1 | |
ENST00000456382.2 | n.103+29T>G | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000264 AC: 4AN: 151766Hom.: 0 Cov.: 28
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GnomAD3 exomes AF: 0.00000988 AC: 1AN: 101208Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 53608
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GnomAD4 exome Cov.: 6
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GnomAD4 genome ? AF: 0.0000264 AC: 4AN: 151766Hom.: 0 Cov.: 28 AF XY: 0.0000135 AC XY: 1AN XY: 74128
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 18, 2021 | The c.1A>C (p.M1?) alteration is located in coding exon 1 of the MSTO1 gene and results from an A to C substitution at nucleotide position 1. This alters the methionine residue at the initiation codon (ATG). Sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on data from the Genome Aggregation Database (gnomAD) database, the MSTO1 c.1A>C alteration was observed in 0% (1/101208) of total alleles studied. This amino acid position is highly conserved in available vertebrate species. Based on the available evidence, this alteration is classified as likely pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
Polyphen
0.95
.;P;.
Vest4
0.81, 0.81
MutPred
Loss of catalytic residue at M1 (P = 0.1244);Loss of catalytic residue at M1 (P = 0.1244);Loss of catalytic residue at M1 (P = 0.1244);
MVP
0.37
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at