Variant 3-38496410-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005107.4(EXOG):c.43C>G(p.Arg15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000173 in 1,614,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

EXOG
NM_005107.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Variant links:

Genes affected

EXOG (HGNC:3347): (exo/endonuclease G) This gene encodes an endo/exonuclease with 5'-3' exonuclease activity. The encoded enzyme catalyzes the hydrolysis of ester linkages at the 5' end of a nucleic acid chain. This enzyme is localized to the mitochondria and may play a role in programmed cell death. Alternatively spliced transcript variants have been described. A pseudogene exists on chromosome 18. [provided by RefSeq, Feb 2009]

EXOG links:

EXOG (HGNC:):

EXOG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02450478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOG	NM_005107.4 linkuse as main transcript	c.43C>G	p.Arg15Gly	missense_variant	1/6	ENST00000287675.10	NP_005098.2	Q9Y2C4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOG	ENST00000287675.10 linkuse as main transcript	c.43C>G	p.Arg15Gly	missense_variant	1/6	1	NM_005107.4	ENSP00000287675.5		Q9Y2C4-1

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000239

AC:

AN:

251018

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000146

AC:

213

AN:

1461724

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00206

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000440

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000792

Hom.:

Bravo

AF:

0.000555

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.0000593

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 09, 2023

The c.43C>G (p.R15G) alteration is located in exon 1 (coding exon 1) of the EXOG gene. This alteration results from a C to G substitution at nucleotide position 43, causing the arginine (R) at amino acid position 15 to be replaced by a glycine (G). 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

0.085

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

T;.;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.025

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

M;.;M

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.7

N;.;N

REVEL

Benign

0.13

Sift

Uncertain

0.0060

D;.;D

Sift4G

Benign

0.17

T;D;D

Polyphen

0.18

B;.;B

Vest4

0.55

MVP

0.27

MPC

0.29

ClinPred

0.11

GERP RS

3.2

Varity_R

0.23

gMVP

0.80

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