9-128818925-T-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_004435.2(ENDOG):āc.241T>Gā(p.Tyr81Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000701 in 1,484,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00011 ( 0 hom., cov: 33)
Exomes š: 0.000066 ( 0 hom. )
Consequence
ENDOG
NM_004435.2 missense
NM_004435.2 missense
Scores
12
4
3
Clinical Significance
Conservation
PhyloP100: 6.81
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.932
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENDOG | NM_004435.2 | c.241T>G | p.Tyr81Asp | missense_variant | 1/3 | ENST00000372642.5 | |
ENDOG | XM_011518347.3 | c.241T>G | p.Tyr81Asp | missense_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENDOG | ENST00000372642.5 | c.241T>G | p.Tyr81Asp | missense_variant | 1/3 | 1 | NM_004435.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 151888Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
16
AN:
151888
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000988 AC: 8AN: 81010Hom.: 0 AF XY: 0.000130 AC XY: 6AN XY: 46192
GnomAD3 exomes
AF:
AC:
8
AN:
81010
Hom.:
AF XY:
AC XY:
6
AN XY:
46192
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000661 AC: 88AN: 1332270Hom.: 0 Cov.: 33 AF XY: 0.0000929 AC XY: 61AN XY: 656674
GnomAD4 exome
AF:
AC:
88
AN:
1332270
Hom.:
Cov.:
33
AF XY:
AC XY:
61
AN XY:
656674
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000105 AC: 16AN: 151888Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74180
GnomAD4 genome
AF:
AC:
16
AN:
151888
Hom.:
Cov.:
33
AF XY:
AC XY:
11
AN XY:
74180
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
4
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 | Jan 26, 2022 | The c.241T>G (p.Y81D) alteration is located in exon 1 (coding exon 1) of the ENDOG gene. This alteration results from a T to G substitution at nucleotide position 241, causing the tyrosine (Y) at amino acid position 81 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.0169);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at