chrX-101346541-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_004085.4(TIMM8A):c.252C>T(p.Thr84=) variant causes a synonymous 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 Likely benign (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000018 ( 0 hom. 2 hem. )
Failed GnomAD Quality Control
Consequence
TIMM8A
NM_004085.4 synonymous
NM_004085.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.677
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_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant X-101346541-G-A is Benign according to our data. Variant chrX-101346541-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 513750.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.677 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TIMM8A | NM_004085.4 | c.252C>T | p.Thr84= | synonymous_variant | 2/2 | ENST00000372902.4 | |
TIMM8A | NM_001145951.2 | c.*1846C>T | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TIMM8A | ENST00000372902.4 | c.252C>T | p.Thr84= | synonymous_variant | 2/2 | 1 | NM_004085.4 | P1 | |
TIMM8A | ENST00000644112.2 | c.*1846C>T | 3_prime_UTR_variant | 2/2 | |||||
TIMM8A | ENST00000647480.1 | n.769C>T | non_coding_transcript_exon_variant | 2/2 | |||||
TIMM8A | ENST00000645279.1 | c.*446C>T | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
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23
GnomAD3 exomes AF: 0.0000109 AC: 2AN: 183505Hom.: 0 AF XY: 0.0000147 AC XY: 1AN XY: 67937
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000182 AC: 2AN: 1097878Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 2AN XY: 363378
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome Cov.: 23
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23
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 22, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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