6-10398416-CT-C
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001372066.1(TFAP2A):c.1320delA(p.Ter440fs) variant causes a frameshift, stop lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
TFAP2A
NM_001372066.1 frameshift, stop_lost
NM_001372066.1 frameshift, stop_lost
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.81
Genes affected
TFAP2A (HGNC:11742): (transcription factor AP-2 alpha) The protein encoded by this gene is a transcription factor that binds the consensus sequence 5'-GCCNNNGGC-3'. The encoded protein functions as either a homodimer or as a heterodimer with similar family members. This protein activates the transcription of some genes while inhibiting the transcription of others. Defects in this gene are a cause of branchiooculofacial syndrome (BOFS). Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Stoplost variant. No alternative stopcodon identified downstream, so we assume a Nonstop Mediated Decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TFAP2A | NM_001372066.1 | c.1320delA | p.Ter440fs | frameshift_variant, stop_lost | 7/7 | ENST00000379613.10 | NP_001358995.1 | |
TFAP2A | NM_001042425.3 | c.1302delA | p.Ter434fs | frameshift_variant, stop_lost | 7/7 | NP_001035890.1 | ||
TFAP2A | NM_001032280.3 | c.1296delA | p.Ter432fs | frameshift_variant, stop_lost | 7/7 | NP_001027451.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TFAP2A | ENST00000379613.10 | c.1320delA | p.Ter440fs | frameshift_variant, stop_lost | 7/7 | 1 | NM_001372066.1 | ENSP00000368933.5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 38
GnomAD4 exome
Cov.:
38
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Neurodevelopmental abnormality Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine | Jun 04, 2020 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at