chr1-23691828-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM1PP3
The NM_000975.5(RPL11):c.5C>T(p.Ala2Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000167 in 1,614,136 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000975.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL11 | NM_000975.5 | c.5C>T | p.Ala2Val | missense_variant, splice_region_variant | 1/6 | ENST00000643754.2 | |
RPL11 | NM_001199802.1 | c.5C>T | p.Ala2Val | missense_variant, splice_region_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL11 | ENST00000643754.2 | c.5C>T | p.Ala2Val | missense_variant, splice_region_variant | 1/6 | NM_000975.5 | A1 | ||
RPL11 | ENST00000374550.8 | c.5C>T | p.Ala2Val | missense_variant, splice_region_variant | 1/6 | 1 | P4 | ||
RPL11 | ENST00000443624.6 | n.23C>T | splice_region_variant, non_coding_transcript_exon_variant | 1/5 | 2 | ||||
RPL11 | ENST00000467075.2 | c.5C>T | p.Ala2Val | missense_variant, NMD_transcript_variant | 1/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152266Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251468Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461870Hom.: 0 Cov.: 33 AF XY: 0.0000206 AC XY: 15AN XY: 727240
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74388
ClinVar
Submissions by phenotype
Diamond-Blackfan anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 579074). This variant has not been reported in the literature in individuals affected with RPL11-related conditions. This variant is present in population databases (rs768850297, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2 of the RPL11 protein (p.Ala2Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at