rs1443187318
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001129.5(AEBP1):c.917dup(p.Tyr306Ter) variant causes a stop gained, frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,451,114 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (â ). Synonymous variant affecting the same amino acid position (i.e. Y306Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001129.5 stop_gained, 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.917dup | p.Tyr306Ter | stop_gained, frameshift_variant | 6/21 | ENST00000223357.8 | |
AEBP1 | XM_011515162.2 | c.917dup | p.Tyr306Ter | stop_gained, frameshift_variant | 6/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AEBP1 | ENST00000223357.8 | c.917dup | p.Tyr306Ter | stop_gained, frameshift_variant | 6/21 | 1 | NM_001129.5 | P1 | |
AEBP1 | ENST00000455443.5 | c.594dup | p.Tyr199Ter | stop_gained, frameshift_variant | 4/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.0000128 AC: 3AN: 234350Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 126998
GnomAD4 exome AF: 0.00000345 AC: 5AN: 1451114Hom.: 0 Cov.: 35 AF XY: 0.00000139 AC XY: 1AN XY: 720990
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, classic-like, 2 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 08, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-UniversitĂ€t Erlangen-NĂŒrnberg | May 31, 2018 | The homozygous c.917dup variant in exon 6 of AEBP1 gene was identified in two Greek siblings with an Ehlers-Danlos Syndrome associated connective tissue disorder. This variant is predicted to directly cause a premature termination codon (p.Tyr306*) and is only present in 2/229,558 alleles in gnomAD. Sanger sequencing of cDNA showed a predominant expression of the normal allele in the carrier mother. This indicates a nonsense-mediated decay of c.917dup allele, suggesting a null variant in the affected individuals. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at