X-55006594-A-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_014481.4(APEX2):āc.716A>Cā(p.His239Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 1,146,023 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H239Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_014481.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APEX2 | NM_014481.4 | c.716A>C | p.His239Pro | missense_variant | 6/6 | ENST00000374987.4 | |
APEX2 | NM_001271748.2 | c.203A>C | p.His68Pro | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APEX2 | ENST00000374987.4 | c.716A>C | p.His239Pro | missense_variant | 6/6 | 1 | NM_014481.4 | P1 | |
APEX2 | ENST00000471758.1 | n.565A>C | non_coding_transcript_exon_variant | 5/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000179 AC: 2AN: 111791Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1AN XY: 33985
GnomAD3 exomes AF: 0.00000782 AC: 1AN: 127952Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 37388
GnomAD4 exome AF: 0.00000580 AC: 6AN: 1034232Hom.: 0 Cov.: 30 AF XY: 0.00000605 AC XY: 2AN XY: 330430
GnomAD4 genome AF: 0.0000179 AC: 2AN: 111791Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1AN XY: 33985
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 04, 2024 | The c.716A>C (p.H239P) alteration is located in exon 6 (coding exon 6) of the APEX2 gene. This alteration results from a A to C substitution at nucleotide position 716, causing the histidine (H) at amino acid position 239 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at