rs41309506
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004085.4(TIMM8A):c.132+158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,172,658 control chromosomes in the GnomAD database, including 160 homozygotes. There are 6,494 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 11 hom., 401 hem., cov: 21)
Exomes 𝑓: 0.018 ( 149 hom. 6093 hem. )
Consequence
TIMM8A
NM_004085.4 intron
NM_004085.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.327
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant X-101348375-T-C is Benign according to our data. Variant chrX-101348375-T-C is described in ClinVar as [Benign]. Clinvar id is 44082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0123 (1348/110006) while in subpopulation NFE AF= 0.0177 (929/52607). AF 95% confidence interval is 0.0167. There are 11 homozygotes in gnomad4. There are 401 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 11 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TIMM8A | NM_004085.4 | c.132+158A>G | intron_variant | ENST00000372902.4 | |||
TIMM8A | NM_001145951.2 | c.*12A>G | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TIMM8A | ENST00000372902.4 | c.132+158A>G | intron_variant | 1 | NM_004085.4 | P1 | |||
TIMM8A | ENST00000644112.2 | c.*12A>G | 3_prime_UTR_variant | 2/2 | |||||
TIMM8A | ENST00000647480.1 | n.201A>G | non_coding_transcript_exon_variant | 1/2 | |||||
TIMM8A | ENST00000645279.1 | c.*12A>G | 3_prime_UTR_variant, NMD_transcript_variant | 2/3 |
Frequencies
GnomAD3 genomes ? AF: 0.0123 AC: 1348AN: 109950Hom.: 11 Cov.: 21 AF XY: 0.0124 AC XY: 400AN XY: 32276
GnomAD3 genomes
?
AF:
AC:
1348
AN:
109950
Hom.:
Cov.:
21
AF XY:
AC XY:
400
AN XY:
32276
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:
GnomAD3 exomes AF: 0.0136 AC: 1669AN: 122550Hom.: 15 AF XY: 0.0134 AC XY: 550AN XY: 41086
GnomAD3 exomes
AF:
AC:
1669
AN:
122550
Hom.:
AF XY:
AC XY:
550
AN XY:
41086
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0175 AC: 18633AN: 1062652Hom.: 149 Cov.: 31 AF XY: 0.0176 AC XY: 6093AN XY: 347068
GnomAD4 exome
AF:
AC:
18633
AN:
1062652
Hom.:
Cov.:
31
AF XY:
AC XY:
6093
AN XY:
347068
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0123 AC: 1348AN: 110006Hom.: 11 Cov.: 21 AF XY: 0.0124 AC XY: 401AN XY: 32342
GnomAD4 genome
?
AF:
AC:
1348
AN:
110006
Hom.:
Cov.:
21
AF XY:
AC XY:
401
AN XY:
32342
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | *12A>G in Exon 02 of TIMM8A: This variant is not expected to have clinical signi ficance because it has been identified in 1.6% (30/1899) of European American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs41309506). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2014 | 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
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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