rs33956927
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001641.4(APEX1):c.721G>A(p.Gly241Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00101 in 1,614,210 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0052 ( 11 hom., cov: 33)
Exomes 𝑓: 0.00057 ( 9 hom. )
Consequence
APEX1
NM_001641.4 missense
NM_001641.4 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 3.93
Genes affected
APEX1 (HGNC:587): (apurinic/apyrimidinic endodeoxyribonuclease 1) The APEX gene encodes the major AP endonuclease in human cells. It encodes the APEX endonuclease, a DNA repair enzyme with apurinic/apyrimidinic (AP) activity. Such AP activity sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. The AP sites are the most frequent pre-mutagenic lesions that can prevent normal DNA replication. Splice variants have been found for this gene; all encode the same protein. Disruptions in the biological functions related to APEX are associated with many various malignancies and neurodegenerative diseases.[provided by RefSeq, Dec 2019]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008568823).
BP6
?
Variant 14-20457272-G-A is Benign according to our data. Variant chr14-20457272-G-A is described in ClinVar as [Benign]. Clinvar id is 709908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00519 (791/152320) while in subpopulation AFR AF= 0.0183 (761/41574). AF 95% confidence interval is 0.0172. There are 11 homozygotes in gnomad4. There are 377 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APEX1 | NM_001641.4 | c.721G>A | p.Gly241Arg | missense_variant | 5/5 | ENST00000216714.8 | |
APEX1 | NM_001244249.2 | c.721G>A | p.Gly241Arg | missense_variant | 5/5 | ||
APEX1 | NM_080648.3 | c.721G>A | p.Gly241Arg | missense_variant | 5/5 | ||
APEX1 | NM_080649.3 | c.721G>A | p.Gly241Arg | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APEX1 | ENST00000216714.8 | c.721G>A | p.Gly241Arg | missense_variant | 5/5 | 1 | NM_001641.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00520 AC: 792AN: 152202Hom.: 11 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00138 AC: 348AN: 251496Hom.: 3 AF XY: 0.00100 AC XY: 136AN XY: 135922
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GnomAD4 exome AF: 0.000575 AC: 840AN: 1461890Hom.: 9 Cov.: 33 AF XY: 0.000498 AC XY: 362AN XY: 727246
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GnomAD4 genome ? AF: 0.00519 AC: 791AN: 152320Hom.: 11 Cov.: 33 AF XY: 0.00506 AC XY: 377AN XY: 74478
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ESP6500AA
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ExAC
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201
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
APEX1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 01, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;N;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
D;D;D;D;T
Sift4G
Benign
T;T;T;T;T
Polyphen
D;D;.;D;.
Vest4
MutPred
Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);.;
MVP
MPC
0.74
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at