chr5-146339164-GA-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_002700.3(POU4F3):c.54del(p.Glu18AspfsTer66) 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: 33)
Consequence
POU4F3
NM_002700.3 frameshift
NM_002700.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.50
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 12 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 5-146339164-GA-G is Pathogenic according to our data. Variant chr5-146339164-GA-G is described in ClinVar as [Pathogenic]. Clinvar id is 1334107.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POU4F3 | NM_002700.3 | c.54del | p.Glu18AspfsTer66 | frameshift_variant | 1/2 | ENST00000646991.2 | |
LOC127814297 | NM_001414499.1 | c.2887del | p.Thr963ProfsTer321 | frameshift_variant | 19/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POU4F3 | ENST00000646991.2 | c.54del | p.Glu18AspfsTer66 | frameshift_variant | 1/2 | NM_002700.3 | P1 | ||
ENST00000515598.1 | n.404-31889del | 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: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 15 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | King Laboratory, University of Washington | Aug 01, 2020 | POU4F3 c.54delA leads to a stop at codon 84. It is homozygous in a Palestinian child with severe to profound hearing loss (Abu Rayyan 2020). The variant is absent from 1300 Palestinian controls and absent from gnomAD v2.1.1. - |
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.