rs869320664
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_004085.4(TIMM8A):c.116del(p.Met39ArgfsTer26) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 22)
Consequence
TIMM8A
NM_004085.4 frameshift
NM_004085.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.62
Genes affected
TIMM8A (HGNC:11817): (translocase of inner mitochondrial membrane 8A) This translocase is involved in the import and insertion of hydrophobic membrane proteins from the cytoplasm into the mitochondrial inner membrane. The gene is mutated in Mohr-Tranebjaerg syndrome/Deafness Dystonia Syndrome (MTS/DDS) and it is postulated that MTS/DDS is a mitochondrial disease caused by a defective mitochondrial protein import system. Defects in this gene also cause Jensen syndrome; an X-linked disease with opticoacoustic nerve atrophy and muscle weakness. This protein, along with TIMM13, forms a 70 kDa heterohexamer. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-101348548-CA-C is Pathogenic according to our data. Variant chrX-101348548-CA-C is described in ClinVar as [Pathogenic]. Clinvar id is 11318.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-101348548-CA-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TIMM8A | NM_004085.4 | c.116del | p.Met39ArgfsTer26 | frameshift_variant | 1/2 | ENST00000372902.4 | |
TIMM8A | NM_001145951.2 | c.116del | p.Met39ArgfsTer17 | frameshift_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TIMM8A | ENST00000372902.4 | c.116del | p.Met39ArgfsTer26 | frameshift_variant | 1/2 | 1 | NM_004085.4 | P1 | |
TIMM8A | ENST00000644112.2 | c.116del | p.Met39ArgfsTer17 | frameshift_variant | 1/2 | ||||
TIMM8A | ENST00000647480.1 | n.27del | non_coding_transcript_exon_variant | 1/2 | |||||
TIMM8A | ENST00000645279.1 | c.116del | p.Met39ArgfsTer17 | frameshift_variant, NMD_transcript_variant | 1/3 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Deafness dystonia syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 1996 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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