rs371633774
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173630.4(RTTN):āc.2881A>Gā(p.Met961Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000606 in 1,502,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 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
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RTTN | NM_173630.4 | c.2881A>G | p.Met961Val | missense_variant | 22/49 | ENST00000640769.2 | NP_775901.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RTTN | ENST00000640769.2 | c.2881A>G | p.Met961Val | missense_variant | 22/49 | 2 | NM_173630.4 | ENSP00000491507.1 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000845 AC: 16AN: 189378Hom.: 0 AF XY: 0.0000951 AC XY: 10AN XY: 105134
GnomAD4 exome AF: 0.0000585 AC: 79AN: 1350182Hom.: 0 Cov.: 21 AF XY: 0.0000578 AC XY: 39AN XY: 675182
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152290Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74470
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 23, 2015 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2021 | The c.2881A>G (p.M961V) alteration is located in exon 22 (coding exon 22) of the RTTN gene. This alteration results from a A to G substitution at nucleotide position 2881, causing the methionine (M) at amino acid position 961 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 13, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 961 of the RTTN protein (p.Met961Val). This variant is present in population databases (rs371633774, gnomAD 0.01%). 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: 212081). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RTTN protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at