Variant 9-128818882-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004435.2(ENDOG):c.198G>C(p.Lys66Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,458,820 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0086 ( 8 hom., cov: 32)

Exomes 𝑓: 0.012 ( 126 hom. )

Consequence

ENDOG
NM_004435.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.38

Variant links:

Genes affected

ENDOG (HGNC:3346): (endonuclease G) The protein encoded by this gene is a nuclear encoded endonuclease that is localized in the mitochondrion. The encoded protein is widely distributed among animals and cleaves DNA at GC tracts. This protein is capable of generating the RNA primers required by DNA polymerase gamma to initiate replication of mitochondrial DNA. [provided by RefSeq, Jul 2008]

ENDOG 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=0.009155095).

BP6

Variant 9-128818882-G-C is Benign according to our data. Variant chr9-128818882-G-C is described in ClinVar as [Benign]. Clinvar id is 3388005.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENDOG	NM_004435.2 linkuse as main transcript	c.198G>C	p.Lys66Asn	missense_variant	1/3	ENST00000372642.5	NP_004426.2	Q14249E5KNL5
ENDOG	XM_011518347.3 linkuse as main transcript	c.198G>C	p.Lys66Asn	missense_variant	1/4		XP_011516649.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENDOG	ENST00000372642.5 linkuse as main transcript	c.198G>C	p.Lys66Asn	missense_variant	1/3	1	NM_004435.2	ENSP00000361725.4		Q14249

Frequencies

GnomAD3 genomes

AF:

0.00860

AC:

1304

AN:

151588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00221

Gnomad AMR

AF:

0.00703

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00969

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.00911

GnomAD3 exomes

AF:

0.00769

AC:

512

AN:

66614

Hom.:

AF XY:

0.00757

AC XY:

294

AN XY:

38822

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00324

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00162

Gnomad FIN exome

AF:

0.00988

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.00984

GnomAD4 exome

AF:

0.0116

AC:

15216

AN:

1307126

Hom.:

126

Cov.:

AF XY:

0.0113

AC XY:

7291

AN XY:

643830

show subpopulations

Gnomad4 AFR exome

AF:

0.00132

Gnomad4 AMR exome

AF:

0.00403

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00184

Gnomad4 FIN exome

AF:

0.0126

Gnomad4 NFE exome

AF:

0.0132

Gnomad4 OTH exome

AF:

0.00921

GnomAD4 genome

AF:

0.00860

AC:

1304

AN:

151694

Hom.:

Cov.:

AF XY:

0.00838

AC XY:

621

AN XY:

74108

show subpopulations

Gnomad4 AFR

AF:

0.00210

Gnomad4 AMR

AF:

0.00702

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00969

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.00901

Alfa

AF:

0.00576

Hom.:

Bravo

AF:

0.00786

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.00700

AC:

ExAC

AF:

0.00172

AC:

Asia WGS

AF:

0.00116

AC:

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

ENDOG: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0092

MetaSVM

Benign

-0.79

MutationAssessor

Benign

2.0

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.17

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.39

MutPred

0.38

Loss of ubiquitination at K66 (P = 0.0067);

MVP

0.53

MPC

0.83

ClinPred

0.016

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.71

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