chr9-122857930-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001100588.3(RC3H2):c.2447G>T(p.Arg816Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R816H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001100588.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RC3H2 | NM_001100588.3 | c.2447G>T | p.Arg816Leu | missense_variant | 13/21 | ENST00000357244.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RC3H2 | ENST00000357244.7 | c.2447G>T | p.Arg816Leu | missense_variant | 13/21 | 5 | NM_001100588.3 | P1 | |
RC3H2 | ENST00000373670.5 | c.2447G>T | p.Arg816Leu | missense_variant | 12/20 | 5 | P1 | ||
RC3H2 | ENST00000423239.6 | c.2447G>T | p.Arg816Leu | missense_variant | 13/18 | 5 | |||
RC3H2 | ENST00000498479.5 | c.*928G>T | 3_prime_UTR_variant, NMD_transcript_variant | 14/22 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460116Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726310
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 16, 2023 | The c.2447G>T (p.R816L) alteration is located in exon 13 (coding exon 12) of the RC3H2 gene. This alteration results from a G to T substitution at nucleotide position 2447, causing the arginine (R) at amino acid position 816 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at