chr14-21288005-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_020366.4(RPGRIP1):c.29G>A(p.Gly10Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,418 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_020366.4 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 |
---|---|---|---|---|---|---|---|---|
RPGRIP1 | NM_020366.4 | c.29G>A | p.Gly10Glu | missense_variant | 2/25 | ENST00000400017.7 | NP_065099.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPGRIP1 | ENST00000400017.7 | c.29G>A | p.Gly10Glu | missense_variant | 2/25 | 1 | NM_020366.4 | ENSP00000382895.2 | ||
RPGRIP1 | ENST00000557771.5 | c.29G>A | p.Gly10Glu | missense_variant | 1/24 | 5 | ENSP00000451219.1 | |||
RPGRIP1 | ENST00000556336.5 | c.29G>A | p.Gly10Glu | missense_variant | 1/21 | 5 | ENSP00000450445.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249234Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135220
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461418Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3AN XY: 727028
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Leber congenital amaurosis 6;C2750720:Cone-rod dystrophy 13 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 27, 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 glutamic acid 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 RPGRIP1-related conditions. This variant is present in population databases (rs756665749, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 10 of the RPGRIP1 protein (p.Gly10Glu). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at