11-85631786-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018480.7(TMEM126B):ā€‹c.181T>Gā€‹(p.Phe61Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000051 in 1,608,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 33)
Exomes š‘“: 0.000053 ( 0 hom. )

Consequence

TMEM126B
NM_018480.7 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.08
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09997827).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TMEM126BNM_018480.7 linkuse as main transcriptc.181T>G p.Phe61Val missense_variant 2/5 ENST00000358867.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMEM126BENST00000358867.11 linkuse as main transcriptc.181T>G p.Phe61Val missense_variant 2/52 NM_018480.7 P1Q8IUX1-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152172
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000163
AC:
4
AN:
244668
Hom.:
0
AF XY:
0.0000302
AC XY:
4
AN XY:
132452
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000358
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000529
AC:
77
AN:
1455862
Hom.:
0
Cov.:
30
AF XY:
0.0000552
AC XY:
40
AN XY:
724174
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000693
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152172
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.0000971
Hom.:
0
Bravo
AF:
0.0000302
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.000273
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 13, 2021The c.181T>G (p.F61V) alteration is located in exon 2 (coding exon 2) of the TMEM126B gene. This alteration results from a T to G substitution at nucleotide position 181, causing the phenylalanine (F) at amino acid position 61 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
0.0060
DANN
Benign
0.63
DEOGEN2
Benign
0.017
.;T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.040
N
LIST_S2
Benign
0.65
T;T;T
M_CAP
Benign
0.0093
T
MetaRNN
Benign
0.10
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
.;M;M
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-2.4
N;N;D
REVEL
Benign
0.13
Sift
Benign
0.21
T;T;T
Sift4G
Uncertain
0.019
D;D;D
Polyphen
0.24
.;B;.
Vest4
0.26
MVP
0.27
MPC
0.072
ClinPred
0.15
T
GERP RS
-5.0
Varity_R
0.056
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs751104967; hg19: chr11-85342830; COSMIC: COSV100729006; COSMIC: COSV100729006; API