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GeneBe

rs1130409

chr14-20456995-T-Achr14-20456995-T-Cchr14-20456995-T-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM2_SupportingBP4_Moderate

The NM_001641(APEX1):c.444T>A(p.Asp148Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Benignin ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

APEX1
NM_001641 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.117

Links

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 33.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.099983275).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
APEX1NM_001641.4 linkuse as main transcriptc.444T>A p.Asp148Glu missense_variant 5/5 ENST00000216714.8
APEX1NM_001244249.2 linkuse as main transcriptc.444T>A p.Asp148Glu missense_variant 5/5
APEX1NM_080648.3 linkuse as main transcriptc.444T>A p.Asp148Glu missense_variant 5/5
APEX1NM_080649.3 linkuse as main transcriptc.444T>A p.Asp148Glu missense_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
APEX1ENST00000216714.8 linkuse as main transcriptc.444T>A p.Asp148Glu missense_variant 5/51 NM_001641.4 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248646
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134488
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000893
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460840
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
726656
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.050
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
Cadd
Benign
6.0
Dann
Benign
0.70
DEOGEN2
Benign
0.16
T;T;T;T;T;T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.45
N
M_CAP
Benign
0.069
D
MetaRNN
Benign
0.10
T;T;T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.63
N;N;.;N;.;.;.
MutationTaster
Benign
1.0
D;N;N;N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.20
N;N;N;N;N;N;N
REVEL
Benign
0.19
Sift
Benign
1.0
T;T;T;T;T;T;T
Sift4G
Benign
1.0
T;T;T;T;T;T;T
Polyphen
0.0
B;B;.;B;.;.;.
Vest4
0.025
MutPred
0.29
Gain of catalytic residue at D148 (P = 0.0041);Gain of catalytic residue at D148 (P = 0.0041);Gain of catalytic residue at D148 (P = 0.0041);Gain of catalytic residue at D148 (P = 0.0041);Gain of catalytic residue at D148 (P = 0.0041);.;.;
MVP
0.70
MPC
0.16
ClinPred
0.027
T
GERP RS
-2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.36

Splicing

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: rs1130409; hg19: chr14-20925154;