Variant 20-18137961-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The ENST00000432901.4(PET117):c.6T>C(p.Ser2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,491,138 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

PET117
ENST00000432901.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.253

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 20-18137961-T-C is Benign according to our data. Variant chr20-18137961-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3041647.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.253 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PET117	NM_001164811.2 linkuse as main transcript	c.6T>C	p.Ser2=	synonymous_variant	1/2	ENST00000432901.4	NP_001158283.1
KAT14	NM_001392073.1 linkuse as main transcript	c.-544T>C		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 linkuse as main transcript	c.6T>C	p.Ser2=	synonymous_variant	1/2	1	NM_001164811.2	ENSP00000397881	P1
KAT14	ENST00000688188.1 linkuse as main transcript	c.-544T>C		5_prime_UTR_variant	1/11		NM_001392073.1	ENSP00000508684	A1

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

200

AN:

151228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00467

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000963

GnomAD3 exomes

AF:

0.000184

AC:

AN:

97670

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

53938

show subpopulations

Gnomad AFR exome

AF:

0.00494

Gnomad AMR exome

AF:

0.000224

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000111

AC:

149

AN:

1339798

Hom.:

Cov.:

AF XY:

0.0000954

AC XY:

AN XY:

660634

show subpopulations

Gnomad4 AFR exome

AF:

0.00443

Gnomad4 AMR exome

AF:

0.000206

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000189

Gnomad4 OTH exome

AF:

0.000304

GnomAD4 genome

AF:

0.00132

AC:

200

AN:

151340

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

AN XY:

73940

show subpopulations

Gnomad4 AFR

AF:

0.00466

Gnomad4 AMR

AF:

0.000394

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000953

Bravo

AF:

0.00154

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PET117-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 06, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.1

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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