rs762710510
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_002700.3(POU4F3):c.836C>G(p.Thr279Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T279T) has been classified as Benign.
Frequency
Consequence
NM_002700.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POU4F3 | NM_002700.3 | c.836C>G | p.Thr279Arg | missense_variant | 2/2 | ENST00000646991.2 | |
LOC127814297 | NM_001414499.1 | c.*705C>G | 3_prime_UTR_variant | 20/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POU4F3 | ENST00000646991.2 | c.836C>G | p.Thr279Arg | missense_variant | 2/2 | NM_002700.3 | P1 | ||
ENST00000515598.1 | n.404-32987G>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727246
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 20, 2017 | The p.Thr279Arg variant in POU4F3 has not been previously reported in individual s with hearing loss and was absent from large population studies. Computational prediction tools and conservation analysis suggest that the p.Thr279Arg variant may impact the protein, though this information is not predictive enough to dete rmine pathogenicity. In summary, the clinical significance of the p.Thr279Arg va riant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at