rs1285225437
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The ENST00000304593.14(MFF):c.284delC(p.Thr95SerfsTer2) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,518 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. T95T) has been classified as Benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
MFF
ENST00000304593.14 frameshift
ENST00000304593.14 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.21
Publications
0 publications found
Genes affected
MFF (HGNC:24858): (mitochondrial fission factor) This is a nuclear gene encoding a protein that functions in mitochondrial and peroxisomal fission. The encoded protein recruits dynamin-1-like protein (DNM1L) to mitochondria. There are multiple pseudogenes for this gene on chromosomes 1, 5, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]
MFF Gene-Disease associations (from GenCC):
- encephalopathy due to defective mitochondrial and peroxisomal fission 2Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- encephalopathy due to mitochondrial and peroxisomal fission defectInheritance: AR Classification: MODERATE Submitted by: ClinGen
- Leigh syndromeInheritance: AR Classification: MODERATE Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-227332520-AC-A is Pathogenic according to our data. Variant chr2-227332520-AC-A is described in ClinVar as Pathogenic. ClinVar VariationId is 545568.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000304593.14. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MFF | NM_001277062.2 | MANE Select | c.284delC | p.Thr95SerfsTer2 | frameshift | Exon 4 of 9 | NP_001263991.1 | ||
| MFF | NM_001277061.2 | c.362delC | p.Thr121SerfsTer2 | frameshift | Exon 5 of 11 | NP_001263990.1 | |||
| MFF | NM_020194.5 | c.362delC | p.Thr121SerfsTer2 | frameshift | Exon 5 of 11 | NP_064579.3 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MFF | ENST00000304593.14 | TSL:2 MANE Select | c.284delC | p.Thr95SerfsTer2 | frameshift | Exon 4 of 9 | ENSP00000304898.10 | ||
| MFF | ENST00000337110.11 | TSL:1 | c.284delC | p.Thr95SerfsTer2 | frameshift | Exon 4 of 8 | ENSP00000338412.7 | ||
| MFF | ENST00000353339.8 | TSL:5 | c.362delC | p.Thr121SerfsTer2 | frameshift | Exon 5 of 11 | ENSP00000302037.4 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152184
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461334Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727020 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461334
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
727020
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33468
American (AMR)
AF:
AC:
0
AN:
44700
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39676
South Asian (SAS)
AF:
AC:
0
AN:
86226
European-Finnish (FIN)
AF:
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111564
Other (OTH)
AF:
AC:
0
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
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2
0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74354 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152184
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74354
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41448
American (AMR)
AF:
AC:
0
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5188
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68024
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Encephalopathy due to defective mitochondrial and peroxisomal fission 2 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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