rs587780444
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_173630.4(RTTN):āc.6535G>Cā(p.Ala2179Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,459,962 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (ā ā ).
Frequency
Consequence
NM_173630.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RTTN | NM_173630.4 | c.6535G>C | p.Ala2179Pro | missense_variant | 48/49 | ENST00000640769.2 | NP_775901.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RTTN | ENST00000640769.2 | c.6535G>C | p.Ala2179Pro | missense_variant | 48/49 | 2 | NM_173630.4 | ENSP00000491507 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000685 AC: 17AN: 248290Hom.: 0 AF XY: 0.000104 AC XY: 14AN XY: 134722
GnomAD4 exome AF: 0.0000274 AC: 40AN: 1459962Hom.: 1 Cov.: 29 AF XY: 0.0000441 AC XY: 32AN XY: 726340
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 26, 2022 | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2179 of the RTTN protein (p.Ala2179Pro). This variant is present in population databases (rs587780444, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with RTTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 130195). 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 | Genetic Services Laboratory, University of Chicago | Mar 13, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at