chr9-4826926-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_005772.5(RCL1):c.277C>T(p.Arg93Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,798 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. R93H) has been classified as Uncertain significance.
Frequency
Consequence
NM_005772.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RCL1 | NM_005772.5 | c.277C>T | p.Arg93Cys | missense_variant | 3/9 | ENST00000381750.9 | |
RCL1 | NM_001286699.2 | c.-90-6228C>T | intron_variant | ||||
RCL1 | NM_001286700.2 | c.-91+3307C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RCL1 | ENST00000381750.9 | c.277C>T | p.Arg93Cys | missense_variant | 3/9 | 1 | NM_005772.5 | P1 | |
RCL1 | ENST00000381732.3 | c.277C>T | p.Arg93Cys | missense_variant | 3/3 | 2 | |||
RCL1 | ENST00000442869.5 | c.-91+3307C>T | intron_variant | 3 | |||||
RCL1 | ENST00000473230.1 | n.213+3307C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251472Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135910
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461798Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727196
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 09, 2023 | The c.277C>T (p.R93C) alteration is located in exon 3 (coding exon 3) of the RCL1 gene. This alteration results from a C to T substitution at nucleotide position 277, causing the arginine (R) at amino acid position 93 to be replaced by a cysteine (C). 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