chr20-18142250-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001164811.2(PET117):c.139C>T(p.Arg47Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000146 in 1,536,864 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 0.00022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 1 hom. )
Consequence
PET117
NM_001164811.2 missense
NM_001164811.2 missense
Scores
3
7
8
Clinical Significance
Conservation
PhyloP100: 4.51
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 Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.012208074).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PET117 | NM_001164811.2 | c.139C>T | p.Arg47Trp | missense_variant | 2/2 | ENST00000432901.4 | NP_001158283.1 | |
KAT14 | NM_001392073.1 | c.-411C>T | 5_prime_UTR_variant | 2/11 | ENST00000688188.1 | NP_001379002.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PET117 | ENST00000432901.4 | c.139C>T | p.Arg47Trp | missense_variant | 2/2 | 1 | NM_001164811.2 | ENSP00000397881 | P1 | |
KAT14 | ENST00000688188.1 | c.-411C>T | 5_prime_UTR_variant | 2/11 | NM_001392073.1 | ENSP00000508684 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000224 AC: 34AN: 151936Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000804 AC: 114AN: 141848Hom.: 1 AF XY: 0.000593 AC XY: 45AN XY: 75862
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GnomAD4 exome AF: 0.000138 AC: 191AN: 1384810Hom.: 1 Cov.: 30 AF XY: 0.000119 AC XY: 81AN XY: 683306
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GnomAD4 genome AF: 0.000224 AC: 34AN: 152054Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15AN XY: 74330
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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 | Jun 22, 2021 | The c.139C>T (p.R47W) alteration is located in exon 2 (coding exon 2) of the PET117 gene. This alteration results from a C to T substitution at nucleotide position 139, causing the arginine (R) at amino acid position 47 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Vest4
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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