Genetic Variant NM_004435.2:c.124G>A (chr9-128818808-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004435.2(ENDOG):c.124G>A(p.Val42Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000939 in 1,278,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V42L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000080 ( 0 hom. )

Consequence

ENDOG
NM_004435.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.510

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1670847).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004435.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENDOG	NM_004435.2	MANE Select	c.124G>A	p.Val42Met	missense	Exon 1 of 3	NP_004426.2	Q14249

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENDOG	ENST00000372642.5	TSL:1 MANE Select	c.124G>A	p.Val42Met	missense	Exon 1 of 3	ENSP00000361725.4	Q14249
	ENDOG	ENST00000854121.1		c.124G>A	p.Val42Met	missense	Exon 1 of 4	ENSP00000524180.1

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150678

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000798

AC:

AN:

1127672

Hom.:

Cov.:

AF XY:

0.00000185

AC XY:

AN XY:

540508

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22662

American (AMR)

AF:

0.00

AC:

AN:

8144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14786

East Asian (EAS)

AF:

0.00

AC:

AN:

25678

South Asian (SAS)

AF:

0.00

AC:

AN:

37082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2988

European-Non Finnish (NFE)

AF:

0.00000952

AC:

AN:

945802

Other (OTH)

AF:

0.00

AC:

AN:

45230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150678

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73498

show subpopulations

African (AFR)

AF:

0.0000485

AC:

AN:

41270

American (AMR)

AF:

0.00

AC:

AN:

15118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10012

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67524

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.608

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.27

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

0.51

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.31

REVEL

Benign

0.056

Sift

Benign

0.23

Sift4G

Benign

0.26

Polyphen

0.63

Vest4

0.088

MutPred

0.29

Gain of MoRF binding (P = 0.1045)

MVP

0.44

MPC

0.30

ClinPred

0.17

GERP RS

1.8

PromoterAI

0.0074

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.037

gMVP

0.40

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over