chr13-48304021-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate
The NM_000321.3(RB1):c.109A>G(p.Ser37Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000518 in 1,467,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S37R) has been classified as Uncertain significance.
Frequency
Consequence
NM_000321.3 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 |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.109A>G | p.Ser37Gly | missense_variant | 1/27 | ENST00000267163.6 | |
RB1 | NM_001407165.1 | c.109A>G | p.Ser37Gly | missense_variant | 1/27 | ||
RB1 | NM_001407166.1 | c.109A>G | p.Ser37Gly | missense_variant | 1/17 | ||
RB1 | NM_001407167.1 | c.109A>G | p.Ser37Gly | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.109A>G | p.Ser37Gly | missense_variant | 1/27 | 1 | NM_000321.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152092Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000547 AC: 72AN: 1315726Hom.: 0 Cov.: 31 AF XY: 0.0000478 AC XY: 31AN XY: 648602
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152092Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74304
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 16, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23516486) - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2024 | The p.S37G variant (also known as c.109A>G), located in coding exon 1 of the RB1 gene, results from an A to G substitution at nucleotide position 109. The serine at codon 37 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
RB1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 18, 2023 | The RB1 c.109A>G variant is predicted to result in the amino acid substitution p.Ser37Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0048% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-48878157-A-G). In ClinVar, this variant has conflicting interpretations including benign and uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/527919/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Retinoblastoma Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at