rs761386458
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_206933.4(USH2A):c.9956C>T(p.Pro3319Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000205 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P3319P) has been classified as Uncertain significance.
Frequency
Consequence
NM_206933.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.9956C>T | p.Pro3319Leu | missense_variant, splice_region_variant | 50/72 | ENST00000307340.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.9956C>T | p.Pro3319Leu | missense_variant, splice_region_variant | 50/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000674083.1 | c.9956C>T | p.Pro3319Leu | missense_variant, splice_region_variant | 50/73 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251248Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135778
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461736Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727156
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 11, 2015 | The p.Pro3319Leu variant in USH2A has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified in 1/66704 of Eur opean chromosomes and 1/11500 Latino chromosomes by the Exome Aggregation Consor tium (ExAC, http://exac.broadinstitute.org). This variant is located in the last three bases of the exon, which is part of the 5? splice region. Computational t ools do not suggest an impact to splicing. However, this information is not pred ictive enough to rule out pathogenicity. In summary, the clinical significance o f the p.Pro3319Leu variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at