rs121913301
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 6P and 2B. PS1_ModeratePM2PM5BP4_Moderate
The NM_000321.3(RB1):c.1072C>G(p.Arg358Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R358Q) has been classified as Likely benign.
Frequency
Consequence
NM_000321.3 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 |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.1072C>G | p.Arg358Gly | missense_variant | 11/27 | ENST00000267163.6 | |
LOC112268118 | XR_002957522.2 | n.122-3573G>C | intron_variant, non_coding_transcript_variant | ||||
RB1 | NM_001407165.1 | c.1072C>G | p.Arg358Gly | missense_variant | 11/27 | ||
RB1 | NM_001407166.1 | c.1072C>G | p.Arg358Gly | missense_variant | 11/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.1072C>G | p.Arg358Gly | missense_variant | 11/27 | 1 | NM_000321.3 | P1 | |
RB1 | ENST00000650461.1 | c.1072C>G | p.Arg358Gly | missense_variant | 11/27 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Retinoblastoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 358 of the RB1 protein (p.Arg358Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with retinoblastoma (PMID: 8776589). ClinVar contains an entry for this variant (Variation ID: 1370241). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RB1 protein function. 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
Publications
No publications associated with this variant yet.