chr9-4826927-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_005772.5(RCL1):c.278G>A(p.Arg93His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,613,930 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. R93C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005772.5 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 |
---|---|---|---|---|---|---|---|
RCL1 | NM_005772.5 | c.278G>A | p.Arg93His | missense_variant | 3/9 | ENST00000381750.9 | |
RCL1 | NM_001286699.2 | c.-90-6227G>A | intron_variant | ||||
RCL1 | NM_001286700.2 | c.-91+3308G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RCL1 | ENST00000381750.9 | c.278G>A | p.Arg93His | missense_variant | 3/9 | 1 | NM_005772.5 | P1 | |
RCL1 | ENST00000381732.3 | c.278G>A | p.Arg93His | missense_variant | 3/3 | 2 | |||
RCL1 | ENST00000442869.5 | c.-91+3308G>A | intron_variant | 3 | |||||
RCL1 | ENST00000473230.1 | n.213+3308G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251476Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135912
GnomAD4 exome AF: 0.0000472 AC: 69AN: 1461826Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31AN XY: 727210
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7AN XY: 74270
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 03, 2022 | The c.278G>A (p.R93H) alteration is located in exon 3 (coding exon 3) of the RCL1 gene. This alteration results from a G to A substitution at nucleotide position 278, causing the arginine (R) at amino acid position 93 to be replaced by a histidine (H). 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