6-166929712-G-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_003730.6(RNASET2):c.647C>G(p.Pro216Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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. P216L) has been classified as Uncertain significance.
Frequency
Consequence
NM_003730.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNASET2 | NM_003730.6 | c.647C>G | p.Pro216Arg | missense_variant | 9/9 | ENST00000508775.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNASET2 | ENST00000508775.6 | c.647C>G | p.Pro216Arg | missense_variant | 9/9 | 1 | NM_003730.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152124Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251400Hom.: 0 AF XY: 0.0000809 AC XY: 11AN XY: 135892
GnomAD4 exome AF: 0.000150 AC: 219AN: 1461846Hom.: 0 Cov.: 31 AF XY: 0.000144 AC XY: 105AN XY: 727230
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74428
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2021 | This sequence change replaces proline with arginine at codon 216 of the RNASET2 protein (p.Pro216Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. This variant is present in population databases (rs200901770, ExAC 0.01%). This variant has not been reported in the literature in individuals with RNASET2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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