20-18137986-C-T

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

Scores

1
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56
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 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
PET117NM_001164811.2 linkuse as main transcriptc.31C>T p.Leu11Phe missense_variant 1/2 ENST00000432901.4 NP_001158283.1
KAT14NM_001392073.1 linkuse as main transcriptc.-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
PET117ENST00000432901.4 linkuse as main transcriptc.31C>T p.Leu11Phe missense_variant 1/21 NM_001164811.2 ENSP00000397881 P1
KAT14ENST00000688188.1 linkuse as main transcriptc.-519C>T 5_prime_UTR_variant 1/11 NM_001392073.1 ENSP00000508684 A1

Frequencies

GnomAD3 genomes
AF:
0.0000855
AC:
13
AN:
152048
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:
0.00213
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000646
AC:
7
AN:
108382
Hom.:
0
AF XY:
0.0000505
AC XY:
3
AN XY:
59378
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000951
Gnomad SAS exome
AF:
0.0000513
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000108
AC:
146
AN:
1354170
Hom.:
1
Cov.:
29
AF XY:
0.000106
AC XY:
71
AN XY:
667892
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00444
Gnomad4 SAS exome
AF:
0.0000395
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.38e-7
Gnomad4 OTH exome
AF:
0.0000177
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152160
Hom.:
0
Cov.:
32
AF XY:
0.0000941
AC XY:
7
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00214
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
Asia WGS
AF:
0.000289
AC:
1
AN:
3474

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 GeneticsFeb 16, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.041
T
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Benign
0.47
N
LIST_S2
Benign
0.74
T
M_CAP
Pathogenic
0.52
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.95
T
MutationTaster
Benign
1.0
D;D;N
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-2.3
N
REVEL
Benign
0.10
Sift
Benign
0.049
D
Sift4G
Benign
0.24
T
Vest4
0.30
MutPred
0.26
Loss of helix (P = 0.0237);
MVP
0.13
ClinPred
0.27
T
GERP RS
5.0
Varity_R
0.41
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: rs572605530; hg19: chr20-18118630; API