rs201882524
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_016492.5(RANGRF):c.434C>T(p.Pro145Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000496 in 1,611,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. P145T) has been classified as Uncertain significance.
Frequency
Consequence
NM_016492.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RANGRF | NM_016492.5 | c.434C>T | p.Pro145Leu | missense_variant | 4/5 | ENST00000226105.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RANGRF | ENST00000226105.11 | c.434C>T | p.Pro145Leu | missense_variant | 4/5 | 1 | NM_016492.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152094Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000131 AC: 33AN: 251022Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135630
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1459758Hom.: 0 Cov.: 31 AF XY: 0.0000468 AC XY: 34AN XY: 725756
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74280
ClinVar
Submissions by phenotype
Cardiac arrhythmia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 28, 2023 | This variant is present in population databases (rs201882524, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RANGRF-related conditions. ClinVar contains an entry for this variant (Variation ID: 403735). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 145 of the RANGRF protein (p.Pro145Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at