chr20-18142250-C-T

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

Scores

3
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51
Variant links:
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]

Genome browser will be placed here

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
PET117NM_001164811.2 linkuse as main transcriptc.139C>T p.Arg47Trp missense_variant 2/2 ENST00000432901.4 NP_001158283.1
KAT14NM_001392073.1 linkuse as main transcriptc.-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
PET117ENST00000432901.4 linkuse as main transcriptc.139C>T p.Arg47Trp missense_variant 2/21 NM_001164811.2 ENSP00000397881 P1
KAT14ENST00000688188.1 linkuse as main transcriptc.-411C>T 5_prime_UTR_variant 2/11 NM_001392073.1 ENSP00000508684 A1

Frequencies

GnomAD3 genomes
AF:
0.000224
AC:
34
AN:
151936
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00154
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000804
AC:
114
AN:
141848
Hom.:
1
AF XY:
0.000593
AC XY:
45
AN XY:
75862
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00415
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000471
Gnomad SAS exome
AF:
0.0000440
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000514
Gnomad OTH exome
AF:
0.000711
GnomAD4 exome
AF:
0.000138
AC:
191
AN:
1384810
Hom.:
1
Cov.:
30
AF XY:
0.000119
AC XY:
81
AN XY:
683306
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00390
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000392
Gnomad4 SAS exome
AF:
0.0000253
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000232
Gnomad4 OTH exome
AF:
0.000173
GnomAD4 genome
AF:
0.000224
AC:
34
AN:
152054
Hom.:
0
Cov.:
33
AF XY:
0.000202
AC XY:
15
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00151
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00155
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000104
Hom.:
1
Bravo
AF:
0.000397
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000958
AC:
2

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 submitterclinical testingAmbry GeneticsJun 22, 2021The 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.23
T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.081
D
MetaRNN
Benign
0.012
T
MetaSVM
Uncertain
-0.036
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-5.9
D
REVEL
Uncertain
0.60
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0040
D
Vest4
0.17
MVP
0.28
ClinPred
0.14
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.46
gMVP
0.23

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: rs76168870; hg19: chr20-18122894; COSMIC: COSV100890039; COSMIC: COSV100890039; API