NM_001009994.3:c.70A>G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001009994.3(RIPPLY2):c.70A>G(p.Thr24Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).
Frequency
Consequence
NM_001009994.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RIPPLY2 | ENST00000369689.6 | c.70A>G | p.Thr24Ala | missense_variant | Exon 1 of 4 | 1 | NM_001009994.3 | ENSP00000358703.1 | ||
ENSG00000287705 | ENST00000656981.1 | n.682T>C | non_coding_transcript_exon_variant | Exon 1 of 1 | ||||||
RIPPLY2 | ENST00000369687.2 | c.-288A>G | upstream_gene_variant | 2 | ENSP00000358701.1 | |||||
RIPPLY2 | ENST00000635617.1 | n.-104A>G | upstream_gene_variant | 6 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1387460Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 684406
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
This variant has not been reported in the literature in individuals with RIPPLY2-related conditions. This sequence change replaces threonine with alanine at codon 24 of the RIPPLY2 protein (p.Thr24Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. 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 alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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
Publications
No publications associated with this variant yet.