1-103536183-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_017619.4(RNPC3):c.613C>T(p.Arg205*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000515 in 1,535,158 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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R205R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_017619.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNPC3 | ENST00000423855.7 | c.613C>T | p.Arg205* | stop_gained | Exon 6 of 15 | 1 | NM_017619.4 | ENSP00000391432.1 | ||
RNPC3 | ENST00000533099.5 | c.613C>T | p.Arg205* | stop_gained | Exon 7 of 16 | 5 | ENSP00000432886.1 | |||
RNPC3 | ENST00000524631.5 | c.613C>T | p.Arg205* | stop_gained | Exon 6 of 15 | 2 | ENSP00000437278.1 | |||
RNPC3 | ENST00000527062.5 | c.136C>T | p.Arg46* | stop_gained | Exon 6 of 8 | 5 | ENSP00000436315.1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152068Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000535 AC: 74AN: 1382972Hom.: 0 Cov.: 29 AF XY: 0.0000484 AC XY: 33AN XY: 682488
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74394
ClinVar
Submissions by phenotype
Isolated growth hormone deficiency, type 5 Pathogenic:1
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not provided Pathogenic:1
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32462814, Gucev2015[Poster], 34906446) -
Decreased response to growth hormone stimulation test Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at