rs727503377
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM4PP5_Moderate
The NM_000307.5(POU3F4):c.1086_*3del variant causes a frameshift, stop lost change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Consequence
POU3F4
NM_000307.5 frameshift, stop_lost
NM_000307.5 frameshift, stop_lost
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.02
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 Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Stoplost variant in NM_000307.5 Downstream stopcodon found after 51 codons.
PP5
?
Variant X-83509406-TCTGA-T is Pathogenic according to our data. Variant chrX-83509406-TCTGA-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 164976.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-83509406-TCTGA-T is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POU3F4 | NM_000307.5 | c.1086_*3del | frameshift_variant, stop_lost | 1/1 | ENST00000644024.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POU3F4 | ENST00000644024.2 | c.1086_*3del | frameshift_variant, stop_lost | 1/1 | NM_000307.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rare genetic deafness Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 27, 2013 | The X362fs variant in POU3F4 has not been previously reported in individuals wit h hearing loss or in large population studies. This nonstop extension variant al ters the normal stop codon at position 362 leading to the addition of 106 amino acids and significant loss of the 3? untranslated region (3'UTR). Two similar ex tension variants in POU3F4, that also cause disruption of the stop codon and los s of the 3?UTR, have been reported in two individuals with hearing loss (Choi 20 13). Functional analyses reveal that these variants alter the protein?s expressi on, localization and function (Choi 2013); however, functional studies are neede d to determine whether the variant in this individual would have the same impact on the protein. In summary, this variant is likely to be pathogenic, though add itional studies are required to fully establish its clinical significance. - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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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