14-21288050-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_020366.4(RPGRIP1):c.74C>T(p.Pro25Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,610,930 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). Synonymous variant affecting the same amino acid position (i.e. P25P) has been classified as Likely benign.
Frequency
Consequence
NM_020366.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPGRIP1 | NM_020366.4 | c.74C>T | p.Pro25Leu | missense_variant | 2/25 | ENST00000400017.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPGRIP1 | ENST00000400017.7 | c.74C>T | p.Pro25Leu | missense_variant | 2/25 | 1 | NM_020366.4 | P2 | |
RPGRIP1 | ENST00000557771.5 | c.74C>T | p.Pro25Leu | missense_variant | 1/24 | 5 | A2 | ||
RPGRIP1 | ENST00000556336.5 | c.74C>T | p.Pro25Leu | missense_variant | 1/21 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000664 AC: 101AN: 152098Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000132 AC: 33AN: 249230Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135212
GnomAD4 exome AF: 0.0000507 AC: 74AN: 1458714Hom.: 0 Cov.: 28 AF XY: 0.0000427 AC XY: 31AN XY: 725884
GnomAD4 genome ? AF: 0.000664 AC: 101AN: 152216Hom.: 0 Cov.: 31 AF XY: 0.000645 AC XY: 48AN XY: 74416
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 11, 2016 | - - |
Leber congenital amaurosis 6;C2750720:Cone-rod dystrophy 13 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 07, 2023 | - - |
Cone-rod dystrophy 13 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Leber congenital amaurosis 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at