5-146339148-GC-G
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_002700.3(POU4F3):c.37del(p.His13ThrfsTer71) variant causes a frameshift change. 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: 33)
Consequence
POU4F3
NM_002700.3 frameshift
NM_002700.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.75
Genes affected
POU4F3 (HGNC:9220): (POU class 4 homeobox 3) This gene encodes a member of the POU-domain family of transcription factors. POU-domain proteins have been observed to play important roles in control of cell identity in several systems. This protein is found in the retina and may play a role in determining or maintaining the identities of a small subset of visual system neurons. Defects in this gene are the cause of non-syndromic sensorineural deafness autosomal dominant type 15. [provided by RefSeq, Mar 2009]
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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 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 43 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-146339148-GC-G is Pathogenic according to our data. Variant chr5-146339148-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 1699941.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POU4F3 | NM_002700.3 | c.37del | p.His13ThrfsTer71 | frameshift_variant | 1/2 | ENST00000646991.2 | |
LOC127814297 | NM_001414499.1 | c.2870del | p.Ala957AspfsTer327 | frameshift_variant | 19/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POU4F3 | ENST00000646991.2 | c.37del | p.His13ThrfsTer71 | frameshift_variant | 1/2 | NM_002700.3 | P1 | ||
ENST00000515598.1 | n.404-31873del | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 15 Pathogenic:1
Pathogenic, no assertion criteria provided | research | Young Lab, Memorial University | Jul 28, 2022 | The c.37del variant in POU4F3 has been identified in a seven generation kindred with variable, progressive autosomal dominant hearing loss, and segregated with disease. Based on the experimental evidence, we classified POU4F3 c.37del as pathogenic, meeting both conservative (PVS1, PM2, PP1_moderate, and PP3) and less conservative (PVS1, PM2, PP1_strong, and PP3) criteria according to the American College of Medical Genetics and Genomics. - |
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
Publications
No publications associated with this variant yet.