chr15-82538986-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001021.6(RPS17):c.156-1G>A variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_001021.6 splice_acceptor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RPS17 | NM_001021.6 | c.156-1G>A | splice_acceptor_variant, intron_variant | Intron 2 of 4 | ENST00000647841.1 | NP_001012.1 | ||
RPS17 | NR_111943.2 | n.478-1G>A | splice_acceptor_variant, intron_variant | Intron 1 of 3 | ||||
RPS17 | NR_111944.3 | n.185-1G>A | splice_acceptor_variant, intron_variant | Intron 2 of 5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPS17 | ENST00000647841.1 | c.156-1G>A | splice_acceptor_variant, intron_variant | Intron 2 of 4 | NM_001021.6 | ENSP00000498019.1 | ||||
ENSG00000260836 | ENST00000562833.2 | c.1503-1G>A | splice_acceptor_variant, intron_variant | Intron 10 of 12 | 3 | ENSP00000454786.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Diamond-Blackfan anemia 4 Pathogenic:1
The c.156-1G>A variant in RPS17(NM_001021.6) has been found in a girl with Diamond-Blackfan anemia phenotype and was absent from large population studies. Additionally, family segregation analysis showed that the variant is de novo. The variant is expected to disrupt normal splicing. In summary, this variant meets our criteria to be classified as likely pathogenic, based on the segregation study, absence from controls, and possible aberrant splicing. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.