rs397516336
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000307.5(POU3F4):c.853_854del(p.Ile285ArgfsTer43) 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 (★).
Frequency
Genomes: not found (cov: 24)
Consequence
POU3F4
NM_000307.5 frameshift
NM_000307.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.29
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 20 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-83509176-CAT-C is Pathogenic according to our data. Variant chrX-83509176-CAT-C is described in ClinVar as [Pathogenic]. Clinvar id is 43352.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-83509176-CAT-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POU3F4 | NM_000307.5 | c.853_854del | p.Ile285ArgfsTer43 | frameshift_variant | 1/1 | ENST00000644024.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POU3F4 | ENST00000644024.2 | c.853_854del | p.Ile285ArgfsTer43 | frameshift_variant | 1/1 | NM_000307.5 | P1 | ||
ENST00000625081.1 | n.37_38del | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
X-linked mixed hearing loss with perilymphatic gusher Pathogenic:1
Pathogenic, no assertion criteria provided | research | Laboratory of Prof. Karen Avraham, Tel Aviv University | May 07, 2018 | X-linked, congenital, profound NSHL; Mondini - |
Rare genetic deafness Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 18, 2012 | The Ile285fs variant in POU3F4 has not been reported in the literature nor previ ously identified by our laboratory. However, this frameshift variant is predicte d to alter the protein?s amino acid sequence beginning at position 285 and lead to a premature termination codon 43 amino acids downstream. This alteration is t hen predicted to lead to a truncated or absent protein. In summary, this variant meets our criteria to be classified as pathogenic (http://pcpgm.partners.org/LM M). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at