2-88691895-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_144563.3(RPIA):āc.197A>Gā(p.Asn66Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,596,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_144563.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RPIA | NM_144563.3 | c.197A>G | p.Asn66Ser | missense_variant | 1/9 | ENST00000283646.5 | NP_653164.2 | |
RPIA | XM_047443733.1 | c.197A>G | p.Asn66Ser | missense_variant | 1/6 | XP_047299689.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPIA | ENST00000283646.5 | c.197A>G | p.Asn66Ser | missense_variant | 1/9 | 1 | NM_144563.3 | ENSP00000283646.3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152062Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000479 AC: 10AN: 208868Hom.: 0 AF XY: 0.0000350 AC XY: 4AN XY: 114214
GnomAD4 exome AF: 0.0000228 AC: 33AN: 1444200Hom.: 0 Cov.: 32 AF XY: 0.0000265 AC XY: 19AN XY: 716652
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152062Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74290
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 28, 2020 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30919572) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 23, 2023 | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1303034). This missense change has been observed in individual(s) with RPIA-related conditions (PMID: 30919572). This variant is present in population databases (rs776100495, gnomAD 0.02%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 66 of the RPIA protein (p.Asn66Ser). 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