chr19-48615440-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_000979.4(RPL18):c.499G>A(p.Val167Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,612,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000979.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL18 | NM_000979.4 | c.499G>A | p.Val167Ile | missense_variant | 7/7 | ENST00000549920.6 | |
RPL18 | NM_001270490.2 | c.412G>A | p.Val138Ile | missense_variant | 6/6 | ||
RPL18 | NR_073022.2 | n.526G>A | non_coding_transcript_exon_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL18 | ENST00000549920.6 | c.499G>A | p.Val167Ile | missense_variant | 7/7 | 1 | NM_000979.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 249894Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135342
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460540Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726416
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74334
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 16, 2023 | This variant is present in population databases (rs774339729, gnomAD 0.01%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with RPL18-related conditions. This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 167 of the RPL18 protein (p.Val167Ile). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at