chr11-85631738-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018480.7(TMEM126B):āc.133G>Cā(p.Asp45His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,108 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
TMEM126B
NM_018480.7 missense
NM_018480.7 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 1.69
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM126B | NM_018480.7 | c.133G>C | p.Asp45His | missense_variant | 2/5 | ENST00000358867.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM126B | ENST00000358867.11 | c.133G>C | p.Asp45His | missense_variant | 2/5 | 2 | NM_018480.7 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461108Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726872
GnomAD4 exome
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1
AN:
1461108
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Cov.:
31
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AC XY:
1
AN XY:
726872
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 24, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with TMEM126B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 45 of the TMEM126B protein (p.Asp45His). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
N;N;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;.
Vest4
MutPred
0.63
.;Loss of ubiquitination at K47 (P = 0.0464);Loss of ubiquitination at K47 (P = 0.0464);
MVP
MPC
0.28
ClinPred
D
GERP RS
Varity_R
gMVP
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
No publications associated with this variant yet.