rs201538234
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_006269.2(RP1):c.2716G>A(p.Ala906Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,613,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. A906P) has been classified as Uncertain significance.
Frequency
Consequence
NM_006269.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RP1 | NM_006269.2 | c.2716G>A | p.Ala906Thr | missense_variant | 4/4 | ENST00000220676.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RP1 | ENST00000220676.2 | c.2716G>A | p.Ala906Thr | missense_variant | 4/4 | 1 | NM_006269.2 | ||
RP1 | ENST00000636932.1 | c.787+4310G>A | intron_variant | 5 | |||||
RP1 | ENST00000637698.1 | c.787+4310G>A | intron_variant | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152072Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000120 AC: 30AN: 249938Hom.: 0 AF XY: 0.0000886 AC XY: 12AN XY: 135512
GnomAD4 exome AF: 0.0000595 AC: 87AN: 1461336Hom.: 0 Cov.: 36 AF XY: 0.0000564 AC XY: 41AN XY: 726964
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152072Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74284
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 23, 2018 | The RP1 c.2716G>A; p.Ala906Thr variant (rs201538234), to our knowledge, is not reported in the medical literature. The variant is reported in the ClinVar database (Variation ID: 167603) and in the general population with an overall allele frequency of 0.01% (29/276206 alleles) in the Genome Aggregation Database. The alanine at codon 906 is weakly conserved but computational analyses predict this variant is deleterious. Considering available information, there is insufficient evidence to classify this variant with certainty. Pathogenic RP1 variants are causative for autosomal dominant or recessive retinitis pigmentosa (MIM: 180100). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 25, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 906 of the RP1 protein (p.Ala906Thr). This variant is present in population databases (rs201538234, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with RP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 167603). 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. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 27, 2014 | - - |
Retinitis pigmentosa 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at