chrX-55002258-C-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_014481.4(APEX2):c.249C>T(p.Ala83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,193,051 control chromosomes in the GnomAD database, including 63 homozygotes. There are 3,697 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0071 ( 4 hom., 202 hem., cov: 23)
Exomes 𝑓: 0.010 ( 59 hom. 3495 hem. )
Consequence
APEX2
NM_014481.4 synonymous
NM_014481.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.957
Genes affected
APEX2 (HGNC:17889): (apurinic/apyrimidinic endodeoxyribonuclease 2) Apurinic/apyrimidinic (AP) sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. AP sites are pre-mutagenic lesions that can prevent normal DNA replication so the cell contains systems to identify and repair such sites. Class II AP endonucleases cleave the phosphodiester backbone 5' to the AP site. This gene encodes a protein shown to have a weak class II AP endonuclease activity. Most of the encoded protein is located in the nucleus but some is also present in mitochondria. This protein may play an important role in both nuclear and mitochondrial base excision repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant X-55002258-C-T is Benign according to our data. Variant chrX-55002258-C-T is described in ClinVar as [Benign]. Clinvar id is 719560.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-55002258-C-T is described in Lovd as [Likely_benign].
BS2
High Homozygotes in GnomAd4 at 4 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APEX2 | NM_014481.4 | c.249C>T | p.Ala83= | synonymous_variant | 3/6 | ENST00000374987.4 | |
APEX2 | NM_001271748.2 | c.-92+629C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APEX2 | ENST00000374987.4 | c.249C>T | p.Ala83= | synonymous_variant | 3/6 | 1 | NM_014481.4 | P1 | |
APEX2 | ENST00000471758.1 | n.271+629C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00708 AC: 796AN: 112364Hom.: 4 Cov.: 23 AF XY: 0.00588 AC XY: 203AN XY: 34528
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GnomAD3 exomes AF: 0.00635 AC: 1006AN: 158422Hom.: 2 AF XY: 0.00555 AC XY: 267AN XY: 48074
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GnomAD4 exome AF: 0.0104 AC: 11287AN: 1080633Hom.: 59 Cov.: 31 AF XY: 0.00995 AC XY: 3495AN XY: 351239
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GnomAD4 genome AF: 0.00707 AC: 795AN: 112418Hom.: 4 Cov.: 23 AF XY: 0.00584 AC XY: 202AN XY: 34592
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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