11-57530174-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012456.3(TIMM10):​c.16G>A​(p.Ala6Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TIMM10
NM_012456.3 missense

Scores

7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.40
Variant links:
Genes affected
TIMM10 (HGNC:11814): (translocase of inner mitochondrial membrane 10) The mitochondrial protein encoded by this gene belongs to a family of evolutionarily conserved proteins that are organized in heterooligomeric complexes in the mitochondrial intermembrane space. These proteins mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane, functioning as intermembrane space chaperones for the highly insoluble carrier proteins. [provided by RefSeq, Nov 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39970198).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TIMM10NM_012456.3 linkc.16G>A p.Ala6Thr missense_variant Exon 2 of 3 ENST00000257245.9 NP_036588.1 P62072
TIMM10XM_024448436.2 linkc.16G>A p.Ala6Thr missense_variant Exon 2 of 3 XP_024304204.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TIMM10ENST00000257245.9 linkc.16G>A p.Ala6Thr missense_variant Exon 2 of 3 1 NM_012456.3 ENSP00000257245.4 P62072
TIMM10ENST00000525158.1 linkc.16G>A p.Ala6Thr missense_variant Exon 2 of 3 2 ENSP00000433627.1 P62072
TIMM10ENST00000525587.1 linkc.16G>A p.Ala6Thr missense_variant Exon 2 of 3 3 ENSP00000435678.1 P62072

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152162
Hom.:
0
Cov.:
32
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461850
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727230
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74322
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Uncertain
0.063
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.064
T;T;T
Eigen
Benign
0.12
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.88
.;.;D
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.40
T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.68
N;N;N
REVEL
Benign
0.20
Sift
Benign
0.12
T;T;T
Sift4G
Benign
0.34
T;T;T
Polyphen
0.0090
B;B;B
Vest4
0.59
MutPred
0.35
Gain of phosphorylation at A6 (P = 0.0488);Gain of phosphorylation at A6 (P = 0.0488);Gain of phosphorylation at A6 (P = 0.0488);
MVP
0.56
MPC
0.44
ClinPred
0.98
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.35
gMVP
0.85

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: rs145077770; hg19: chr11-57297647; API