rs1555639076
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_182641.4(BPTF):c.2366del(p.Asn789ThrfsTer36) variant causes a frameshift 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
BPTF
NM_182641.4 frameshift
NM_182641.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.13
Genes affected
BPTF (HGNC:3581): (bromodomain PHD finger transcription factor) This gene was identified by the reactivity of its encoded protein to a monoclonal antibody prepared against brain homogenates from patients with Alzheimer's disease. Analysis of the original protein (fetal Alz-50 reactive clone 1, or FAC1), identified as an 810 aa protein containing a DNA-binding domain and a zinc finger motif, suggested it might play a role in the regulation of transcription. High levels of FAC1 were detected in fetal brain and in patients with neurodegenerative diseases. The protein encoded by this gene is actually much larger than originally thought, and it also contains a C-terminal bromodomain characteristic of proteins that regulate transcription during proliferation. The encoded protein is highly similar to the largest subunit of the Drosophila NURF (nucleosome remodeling factor) complex. In Drosophila, the NURF complex, which catalyzes nucleosome sliding on DNA and interacts with sequence-specific transcription factors, is necessary for the chromatin remodeling required for transcription. Two alternative transcripts encoding different isoforms have been described completely. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 17-67893676-GA-G is Pathogenic according to our data. Variant chr17-67893676-GA-G is described in ClinVar as [Pathogenic]. Clinvar id is 431073.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-67893676-GA-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BPTF | NM_182641.4 | c.2366del | p.Asn789ThrfsTer36 | frameshift_variant | 6/28 | ENST00000306378.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BPTF | ENST00000306378.11 | c.2366del | p.Asn789ThrfsTer36 | frameshift_variant | 6/28 | 1 | NM_182641.4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 13, 2020 | The alteration results in a premature stop codon: _x000D_ _x000D_ The c.2366delA (p.N789Tfs*36) alteration, located in coding exon 6 of the BPTF gene, results from a deletion of 1 nucleotide at position 2366, causing a translational frameshift with a predicted alternate stop codon after 36 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on the available evidence, this alteration is classified as pathogenic. - |
Secondary microcephaly;C0454641:Expressive language delay;C0557874:Global developmental delay Pathogenic:1
Pathogenic, no assertion criteria provided | research | Baylor Genetics | Jul 03, 2017 | This frameshift variant was found de novo in a 12-year-old female with mild intellectual disability, hypotonia, postnatal microcephaly, dysmorphic features, failure to thrive, GI dysmotility, pain amplification syndrome. - |
Computational scores
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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