20-18142268-C-T

Position:

chr20-18142268-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000432901.4(PET117):c.157C>T(p.Arg53Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,537,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R53G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

PET117
ENST00000432901.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.14

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]

PET117 links:

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]

KAT14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31744236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PET117	NM_001164811.2 linkuse as main transcript	c.157C>T	p.Arg53Cys	missense_variant	2/2	ENST00000432901.4	NP_001158283.1
KAT14	NM_001392073.1 linkuse as main transcript	c.-393C>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 linkuse as main transcript	c.157C>T	p.Arg53Cys	missense_variant	2/2	1	NM_001164811.2	ENSP00000397881	P1
KAT14	ENST00000688188.1 linkuse as main transcript	c.-393C>T		5_prime_UTR_variant	2/11		NM_001392073.1	ENSP00000508684	A1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000493

AC:

AN:

141868

Hom.:

AF XY:

0.0000659

AC XY:

AN XY:

75876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000407

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000116

AC:

160

AN:

1384848

Hom.:

Cov.:

AF XY:

0.0000907

AC XY:

AN XY:

683344

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000841

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.0000863

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000680

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

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

Nov 08, 2021

The c.157C>T (p.R53C) 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 157, causing the arginine (R) at amino acid position 53 to be replaced by a cysteine (C). 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

0.23

BayesDel_addAF

Benign

-0.0015

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.079

Eigen

Benign

0.14

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.018

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.39

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.30

Sift

Benign

0.034

Sift4G

Uncertain

0.048

Vest4

0.56

MVP

0.39

ClinPred

0.24

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over