rs1555984570
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000307.5(POU3F4):c.648del(p.Leu217TrpfsTer24) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 23)
Consequence
POU3F4
NM_000307.5 frameshift
NM_000307.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.59
Genes affected
POU3F4 (HGNC:9217): (POU class 3 homeobox 4) This gene encodes a member of the POU-III class of neural transcription factors. This family member plays a role in inner ear development. The protein is thought to be involved in the mediation of epigenetic signals which induce striatal neuron-precursor differentiation. Mutations in this gene are associated with X chromosome-linked nonsyndromic mixed deafness. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 26 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-83508968-TG-T is Pathogenic according to our data. Variant chrX-83508968-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 11677.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-83508968-TG-T is described in Lovd as [Pathogenic]. Variant chrX-83508968-TG-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POU3F4 | NM_000307.5 | c.648del | p.Leu217TrpfsTer24 | frameshift_variant | 1/1 | ENST00000644024.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POU3F4 | ENST00000644024.2 | c.648del | p.Leu217TrpfsTer24 | frameshift_variant | 1/1 | NM_000307.5 | P1 | ||
ENST00000625081.1 | n.246del | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
X-linked mixed hearing loss with perilymphatic gusher Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 03, 1995 | - - |
Computational scores
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Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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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