chr21-42475911-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_080860.4(RSPH1):āc.864T>Gā(p.Tyr288*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,610,188 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 (ā ).
Frequency
Consequence
NM_080860.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RSPH1 | NM_080860.4 | c.864T>G | p.Tyr288* | stop_gained | Exon 8 of 9 | ENST00000291536.8 | NP_543136.1 | |
RSPH1 | NM_001286506.2 | c.750T>G | p.Tyr250* | stop_gained | Exon 7 of 8 | NP_001273435.1 | ||
RSPH1 | XM_011529786.2 | c.792T>G | p.Tyr264* | stop_gained | Exon 7 of 8 | XP_011528088.1 | ||
RSPH1 | XM_005261208.3 | c.657T>G | p.Tyr219* | stop_gained | Exon 6 of 7 | XP_005261265.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RSPH1 | ENST00000291536.8 | c.864T>G | p.Tyr288* | stop_gained | Exon 8 of 9 | 1 | NM_080860.4 | ENSP00000291536.3 | ||
RSPH1 | ENST00000398352.3 | c.750T>G | p.Tyr250* | stop_gained | Exon 7 of 8 | 5 | ENSP00000381395.3 | |||
RSPH1 | ENST00000493019.1 | n.2482T>G | non_coding_transcript_exon_variant | Exon 7 of 8 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000674 AC: 1AN: 148344Hom.: 0 Cov.: 28
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251436Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135894
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461844Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727234
GnomAD4 genome AF: 0.00000674 AC: 1AN: 148344Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 72054
ClinVar
Submissions by phenotype
not provided Uncertain:1
Nonsense variant predicted to result in protein truncation as the last 22 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at