X-48893945-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001395498.1(TIMM17B):c.385G>A(p.Val129Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000255 in 1,096,674 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000026 ( 0 hom. 9 hem. )
Failed GnomAD Quality Control
Consequence
TIMM17B
NM_001395498.1 missense
NM_001395498.1 missense
Scores
4
13
Clinical Significance
Conservation
PhyloP100: 3.96
Genes affected
TIMM17B (HGNC:17310): (translocase of inner mitochondrial membrane 17B) This gene encodes a multipass transmembrane protein that forms an integral component of the mitochondrial translocase TIM23 complex. This complex facilitates the transport of mitochondrial proteins from the cytosol across the mitochondrial inner membrane and into the mitochondrion. There is a pseudogene for this gene on chromosome 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
PQBP1 (HGNC:9330): (polyglutamine binding protein 1) This gene encodes a nuclear polyglutamine-binding protein that is involved with transcription activation. The encoded protein contains a WW domain. Mutations in this gene have been found in patients with Renpenning syndrome 1 and other syndromes with X-linked cognitive disability. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.[provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.3284304).
BS2
High Hemizygotes in GnomAdExome4 at 9 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TIMM17B | NM_001395498.1 | c.385G>A | p.Val129Ile | missense_variant | 5/6 | ENST00000696123.1 | |
TIMM17B | NM_001167947.2 | c.535G>A | p.Val179Ile | missense_variant | 7/8 | ||
TIMM17B | NM_001395497.1 | c.535G>A | p.Val179Ile | missense_variant | 6/7 | ||
TIMM17B | NM_005834.5 | c.385G>A | p.Val129Ile | missense_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TIMM17B | ENST00000696123.1 | c.385G>A | p.Val129Ile | missense_variant | 5/6 | NM_001395498.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 2AN: 112365Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1AN XY: 34545 FAILED QC
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GnomAD3 exomes AF: 0.0000222 AC: 4AN: 180013Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 64947
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GnomAD4 exome AF: 0.0000255 AC: 28AN: 1096674Hom.: 0 Cov.: 30 AF XY: 0.0000249 AC XY: 9AN XY: 362084
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000178 AC: 2AN: 112365Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1AN XY: 34545
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 09, 2021 | The c.535G>A (p.V179I) alteration is located in exon 7 (coding exon 6) of the TIMM17B gene. This alteration results from a G to A substitution at nucleotide position 535, causing the valine (V) at amino acid position 179 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;.;T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
.;N;N;.
REVEL
Benign
Sift
Benign
.;T;D;.
Sift4G
Benign
T;T;T;T
Polyphen
0.35
.;B;.;.
Vest4
MutPred
0.65
.;Loss of catalytic residue at V129 (P = 0.2383);.;.;
MVP
MPC
0.48
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at