20-18137986-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000432901.4(PET117):c.31C>T(p.Leu11Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,506,330 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 1 hom. )
Consequence
PET117
ENST00000432901.4 missense
ENST00000432901.4 missense
Scores
1
4
13
Clinical Significance
Conservation
PhyloP100: 1.56
Genes affected
PET117 (HGNC:40045): (PET117 cytochrome c oxidase chaperone) Predicted to be involved in mitochondrial cytochrome c oxidase assembly. Located in mitochondrion. Implicated in cytochrome-c oxidase deficiency disease. [provided by Alliance of Genome Resources, Apr 2022]
KAT14 (HGNC:15904): (lysine acetyltransferase 14) CSRP2 is a protein containing two LIM domains, which are double zinc finger motifs found in proteins of diverse function. CSRP2 and some related proteins are thought to act as protein adapters, bridging two or more proteins to form a larger protein complex. The protein encoded by this gene binds to one of the LIM domains of CSRP2 and contains an acetyltransferase domain. Although the encoded protein has been detected in the cytoplasm, it is predominantly a nuclear protein. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jun 2011]
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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=0.11744249).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PET117 | NM_001164811.2 | c.31C>T | p.Leu11Phe | missense_variant | 1/2 | ENST00000432901.4 | NP_001158283.1 | |
KAT14 | NM_001392073.1 | c.-519C>T | 5_prime_UTR_variant | 1/11 | ENST00000688188.1 | NP_001379002.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PET117 | ENST00000432901.4 | c.31C>T | p.Leu11Phe | missense_variant | 1/2 | 1 | NM_001164811.2 | ENSP00000397881 | P1 | |
KAT14 | ENST00000688188.1 | c.-519C>T | 5_prime_UTR_variant | 1/11 | NM_001392073.1 | ENSP00000508684 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000855 AC: 13AN: 152048Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000646 AC: 7AN: 108382Hom.: 0 AF XY: 0.0000505 AC XY: 3AN XY: 59378
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GnomAD4 exome AF: 0.000108 AC: 146AN: 1354170Hom.: 1 Cov.: 29 AF XY: 0.000106 AC XY: 71AN XY: 667892
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GnomAD4 genome AF: 0.0000789 AC: 12AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74394
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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 | Feb 16, 2023 | The c.31C>T (p.L11F) alteration is located in exon 1 (coding exon 1) of the PET117 gene. This alteration results from a C to T substitution at nucleotide position 31, causing the leucine (L) at amino acid position 11 to be replaced by a phenylalanine (F). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Sift4G
Benign
T
Vest4
MutPred
Loss of helix (P = 0.0237);
MVP
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