rs869320666
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_004085.4(TIMM8A):c.133-23A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: not found (cov: 23)
Consequence
TIMM8A
NM_004085.4 intron
NM_004085.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.718
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-101346683-T-G is Pathogenic according to our data. Variant chrX-101346683-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 11325.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-101346683-T-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TIMM8A | NM_004085.4 | c.133-23A>C | intron_variant | ENST00000372902.4 | |||
TIMM8A | NM_001145951.2 | c.*1704A>C | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TIMM8A | ENST00000372902.4 | c.133-23A>C | intron_variant | 1 | NM_004085.4 | P1 | |||
TIMM8A | ENST00000644112.2 | c.*1704A>C | 3_prime_UTR_variant | 2/2 | |||||
TIMM8A | ENST00000645279.1 | c.*327-23A>C | intron_variant, NMD_transcript_variant | ||||||
TIMM8A | ENST00000647480.1 | n.650-23A>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
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 | Feb 01, 2005 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
La Branchor
?
BranchPoint Hunter
?
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 11
Find out detailed SpliceAI scores and Pangolin per-transcript scores at