rs763036623

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001641.4(APEX1):​c.700C>A​(p.Pro234Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

APEX1
NM_001641.4 missense

Scores

1
11
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.81
Variant links:
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APEX1NM_001641.4 linkc.700C>A p.Pro234Thr missense_variant Exon 5 of 5 ENST00000216714.8 NP_001632.2 P27695Q5TZP7
APEX1NM_001244249.2 linkc.700C>A p.Pro234Thr missense_variant Exon 5 of 5 NP_001231178.1 P27695Q5TZP7
APEX1NM_080648.3 linkc.700C>A p.Pro234Thr missense_variant Exon 5 of 5 NP_542379.1 P27695Q5TZP7
APEX1NM_080649.3 linkc.700C>A p.Pro234Thr missense_variant Exon 5 of 5 NP_542380.1 P27695Q5TZP7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APEX1ENST00000216714.8 linkc.700C>A p.Pro234Thr missense_variant Exon 5 of 5 1 NM_001641.4 ENSP00000216714.3 P27695

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251492
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461890
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.050
T
BayesDel_noAF
Benign
-0.13
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.46
T;T;T;T;.
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Benign
0.65
D
LIST_S2
Pathogenic
0.98
.;.;D;D;D
M_CAP
Uncertain
0.087
D
MetaRNN
Uncertain
0.54
D;D;D;D;D
MetaSVM
Uncertain
0.23
D
MutationAssessor
Uncertain
2.4
M;M;.;M;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-2.4
N;N;N;N;N
REVEL
Uncertain
0.32
Sift
Benign
0.15
T;T;D;T;T
Sift4G
Benign
0.18
T;T;T;T;T
Polyphen
0.87
P;P;.;P;.
Vest4
0.55
MutPred
0.50
Gain of catalytic residue at A230 (P = 0.0019);Gain of catalytic residue at A230 (P = 0.0019);Gain of catalytic residue at A230 (P = 0.0019);Gain of catalytic residue at A230 (P = 0.0019);.;
MVP
0.92
MPC
0.39
ClinPred
0.46
T
GERP RS
5.8
Varity_R
0.62
gMVP
0.52

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.

Other links and lift over

dbSNP: rs763036623; hg19: chr14-20925410; API