chr7-44104877-CG-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001129.5(AEBP1):c.218del(p.Gly73AlafsTer219) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,408,012 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. A71A) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001129.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AEBP1 | NM_001129.5 | c.218del | p.Gly73AlafsTer219 | frameshift_variant | 1/21 | ENST00000223357.8 | |
AEBP1 | XM_011515162.2 | c.218del | p.Gly73AlafsTer219 | frameshift_variant | 1/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AEBP1 | ENST00000223357.8 | c.218del | p.Gly73AlafsTer219 | frameshift_variant | 1/21 | 1 | NM_001129.5 | P1 | |
AEBP1 | ENST00000455443.5 | c.90del | p.Gly31AlafsTer154 | frameshift_variant | 1/6 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000192 AC: 3AN: 156182Hom.: 0 AF XY: 0.0000235 AC XY: 2AN XY: 85236
GnomAD4 exome AF: 0.00000213 AC: 3AN: 1408012Hom.: 0 Cov.: 32 AF XY: 0.00000287 AC XY: 2AN XY: 695668
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 12, 2023 | This sequence change creates a premature translational stop signal (p.Gly73Alafs*219) in the AEBP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AEBP1 are known to be pathogenic (PMID: 29606302). This variant is present in population databases (rs112298043, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with AEBP1-related conditions. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at