rs1555652383
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_182641.4(BPTF):c.4838_4839del(p.Val1613GlyfsTer96) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). 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: 1.55
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 Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 17-67912719-CTG-C is Pathogenic according to our data. Variant chr17-67912719-CTG-C is described in ClinVar as [Pathogenic]. Clinvar id is 431065.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-67912719-CTG-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BPTF | NM_182641.4 | c.4838_4839del | p.Val1613GlyfsTer96 | frameshift_variant | 11/28 | ENST00000306378.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BPTF | ENST00000306378.11 | c.4838_4839del | p.Val1613GlyfsTer96 | frameshift_variant | 11/28 | 1 | NM_182641.4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Secondary microcephaly;C0454641:Expressive language delay;C0557874:Global developmental delay Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Baylor Genetics | Jul 03, 2017 | This frameshift variant has been observed once in our laboratory in a 7-year-old male with small stature, microcephaly, minor dysmorphisms, pes planus, severe developmental and speech delay. Mother was negative for variant, father unavailable. - |
Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 07, 2017 | - - |
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