9-4823587-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001286700.2(RCL1):c.-123C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,462 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 (★).
Frequency
Consequence
NM_001286700.2 5_prime_UTR_premature_start_codon_gain
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RCL1 | NM_005772.5 | c.176C>T | p.Thr59Met | missense_variant | Exon 2 of 9 | ENST00000381750.9 | NP_005763.3 | |
RCL1 | NM_001286700.2 | c.-123C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 2 of 8 | NP_001273629.1 | |||
RCL1 | NM_001286700.2 | c.-123C>T | 5_prime_UTR_variant | Exon 2 of 8 | NP_001273629.1 | |||
RCL1 | NM_001286699.2 | c.-90-9567C>T | intron_variant | Intron 1 of 6 | NP_001273628.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248692Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134552
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1459462Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4AN XY: 726060
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.176C>T (p.T59M) alteration is located in exon 2 (coding exon 2) of the RCL1 gene. This alteration results from a C to T substitution at nucleotide position 176, causing the threonine (T) at amino acid position 59 to be replaced by a methionine (M). 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