rs886037835
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_018480.7(TMEM126B):c.401delA(p.Asn134IlefsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000896 in 1,451,394 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000090 ( 0 hom. )
Consequence
TMEM126B
NM_018480.7 frameshift
NM_018480.7 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.730
Publications
4 publications found
Genes affected
TMEM126B (HGNC:30883): (transmembrane protein 126B) This gene encodes a mitochondrial transmembrane protein which is a component of the mitochondrial complex I assembly complex. The encoded protein serves as an assembly factor that is required for formation of the membrane arm of the complex. It interacts with NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 13. Naturally occurring mutations in this gene are associated with isolated complex I deficiency. A pseudogene of this gene has been defined on chromosome 9. [provided by RefSeq, Apr 2017]
TMEM126B Gene-Disease associations (from GenCC):
- mitochondrial complex I deficiency, nuclear type 29Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
- mitochondrial diseaseInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- mitochondrial complex I deficiencyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 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 11-85635668-TA-T is Pathogenic according to our data. Variant chr11-85635668-TA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 236208.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_018480.7. 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 |
|---|---|---|---|---|---|---|---|---|---|
| TMEM126B | NM_018480.7 | MANE Select | c.401delA | p.Asn134IlefsTer2 | frameshift | Exon 4 of 5 | NP_060950.3 | ||
| TMEM126B | NM_001193537.3 | c.341delA | p.Asn114IlefsTer2 | frameshift | Exon 5 of 6 | NP_001180466.1 | |||
| TMEM126B | NM_001193538.3 | c.311delA | p.Asn104IlefsTer2 | frameshift | Exon 5 of 6 | NP_001180467.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TMEM126B | ENST00000358867.11 | TSL:2 MANE Select | c.401delA | p.Asn134IlefsTer2 | frameshift | Exon 4 of 5 | ENSP00000351737.7 | ||
| TMEM126B | ENST00000393375.5 | TSL:1 | c.311delA | p.Asn104IlefsTer2 | frameshift | Exon 5 of 6 | ENSP00000377039.1 | ||
| TMEM126B | ENST00000529197.1 | TSL:1 | n.*450delA | non_coding_transcript_exon | Exon 5 of 6 | ENSP00000436813.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000896 AC: 13AN: 1451394Hom.: 0 Cov.: 30 AF XY: 0.00000554 AC XY: 4AN XY: 721992 show subpopulations
GnomAD4 exome
AF:
AC:
13
AN:
1451394
Hom.:
Cov.:
30
AF XY:
AC XY:
4
AN XY:
721992
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33010
American (AMR)
AF:
AC:
0
AN:
41774
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25926
East Asian (EAS)
AF:
AC:
0
AN:
39330
South Asian (SAS)
AF:
AC:
0
AN:
83798
European-Finnish (FIN)
AF:
AC:
0
AN:
53298
Middle Eastern (MID)
AF:
AC:
0
AN:
5736
European-Non Finnish (NFE)
AF:
AC:
13
AN:
1108610
Other (OTH)
AF:
AC:
0
AN:
59912
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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4
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8
10
<30
30-35
35-40
40-45
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Mitochondrial complex I deficiency, nuclear type 29 Pathogenic:1
Dec 13, 2018
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
Mitochondrial disease Pathogenic:1
May 18, 2016
Wellcome Centre for Mitochondrial Research, Newcastle University
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:clinical testing
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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