Variant 12-57956835-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000300145.4(ATP23):c.686C>T(p.Ala229Val) variant causes a missense change. The variant allele was found at a frequency of 0.00623 in 1,613,702 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 47 hom. )

Consequence

ATP23
ENST00000300145.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.60

Variant links:

Genes affected

ATP23 (HGNC:29452): (ATP23 metallopeptidase and ATP synthase assembly factor homolog) The protein encoded by this gene is amplified in glioblastomas and interacts with the DNA binding subunit of DNA-dependent protein kinase. This kinase is involved in double-strand break repair (DSB), and higher expression of the encoded protein increases the efficiency of DSB. In addition, comparison to orthologous proteins strongly suggests that this protein is a metalloprotease important in the biosynthesis of mitochondrial ATPase. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ATP23 links:

ATP23 (HGNC:):

ATP23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061927736).

BP6

Variant 12-57956835-C-T is Benign according to our data. Variant chr12-57956835-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2643153.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 47 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP23	NM_033276.4 linkuse as main transcript	c.686C>T	p.Ala229Val	missense_variant	6/6	ENST00000300145.4	NP_150592.1	Q9Y6H3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP23	ENST00000300145.4 linkuse as main transcript	c.686C>T	p.Ala229Val	missense_variant	6/6	1	NM_033276.4	ENSP00000300145.3		Q9Y6H3

Frequencies

GnomAD3 genomes

AF:

0.00512

AC:

778

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000851

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00779

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00547

AC:

1364

AN:

249182

Hom.:

AF XY:

0.00547

AC XY:

740

AN XY:

135188

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00642

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00173

Gnomad FIN exome

AF:

0.00121

Gnomad NFE exome

AF:

0.00768

Gnomad OTH exome

AF:

0.00794

GnomAD4 exome

AF:

0.00634

AC:

9271

AN:

1461496

Hom.:

Cov.:

AF XY:

0.00636

AC XY:

4625

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00712

Gnomad4 ASJ exome

AF:

0.0124

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00177

Gnomad4 FIN exome

AF:

0.00157

Gnomad4 NFE exome

AF:

0.00708

Gnomad4 OTH exome

AF:

0.00702

GnomAD4 genome

AF:

0.00511

AC:

778

AN:

152206

Hom.:

Cov.:

AF XY:

0.00472

AC XY:

351

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000851

Gnomad4 NFE

AF:

0.00779

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00738

Hom.:

Bravo

AF:

0.00604

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.00109

AC:

ESP6500EA

AF:

0.00723

AC:

ExAC

AF:

0.00531

AC:

641

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00873

EpiControl

AF:

0.0102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

ATP23: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

Eigen

Benign

-0.050

Eigen_PC

Benign

0.089

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.024

MetaRNN

Benign

0.0062

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.84

REVEL

Benign

0.12

Sift

Uncertain

0.011

Sift4G

Uncertain

0.046

Polyphen

0.13

Vest4

0.40

MVP

0.61

MPC

0.87

ClinPred

0.049

GERP RS

4.7

Varity_R

0.22

gMVP

0.76

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