6-24848117-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001286445.3(RIPOR2):c.1072G>A(p.Ala358Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,613,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. A358S) has been classified as Benign.
Frequency
Consequence
NM_001286445.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RIPOR2 | NM_001286445.3 | c.1072G>A | p.Ala358Thr | missense_variant | 12/22 | ENST00000643898.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RIPOR2 | ENST00000643898.2 | c.1072G>A | p.Ala358Thr | missense_variant | 12/22 | NM_001286445.3 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000563 AC: 14AN: 248672Hom.: 0 AF XY: 0.0000667 AC XY: 9AN XY: 134922
GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461468Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37AN XY: 726992
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with FAM65B-related conditions. This variant is present in population databases (rs35254980, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 329 of the FAM65B protein (p.Ala329Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at