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14-20457496-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001641.4(APEX1):c.945C>T(p.Tyr315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,614,022 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 10 hom. )

Consequence

APEX1
NM_001641.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0200
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 Benign. Variant got -7 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-20457496-C-T is Benign according to our data. Variant chr14-20457496-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 730773.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.02 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
APEX1NM_001641.4 linkuse as main transcriptc.945C>T p.Tyr315= synonymous_variant 5/5 ENST00000216714.8
APEX1NM_001244249.2 linkuse as main transcriptc.945C>T p.Tyr315= synonymous_variant 5/5
APEX1NM_080648.3 linkuse as main transcriptc.945C>T p.Tyr315= synonymous_variant 5/5
APEX1NM_080649.3 linkuse as main transcriptc.945C>T p.Tyr315= synonymous_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
APEX1ENST00000216714.8 linkuse as main transcriptc.945C>T p.Tyr315= synonymous_variant 5/51 NM_001641.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00147
AC:
223
AN:
152188
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.00141
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00275
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.00127
AC:
318
AN:
251276
Hom.:
0
AF XY:
0.00138
AC XY:
188
AN XY:
135834
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000849
Gnomad FIN exome
AF:
0.000836
Gnomad NFE exome
AF:
0.00221
Gnomad OTH exome
AF:
0.00261
GnomAD4 exome
AF:
0.00186
AC:
2715
AN:
1461716
Hom.:
10
Cov.:
33
AF XY:
0.00190
AC XY:
1384
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000823
Gnomad4 FIN exome
AF:
0.000976
Gnomad4 NFE exome
AF:
0.00223
Gnomad4 OTH exome
AF:
0.00147
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00146
AC:
223
AN:
152306
Hom.:
1
Cov.:
32
AF XY:
0.00138
AC XY:
103
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.00141
Gnomad4 NFE
AF:
0.00275
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.00212
Hom.:
1
Bravo
AF:
0.00111
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00196
EpiControl
AF:
0.00142

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeMay 02, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
Cadd
Benign
3.4
Dann
Benign
0.79
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs61752835; hg19: chr14-20925655; API