chr13-48381322-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000321.3(RB1):c.1574C>A(p.Ala525Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,728 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. A525T) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.1574C>A | p.Ala525Asp | missense_variant | 17/27 | ENST00000267163.6 | |
RB1 | NM_001407165.1 | c.1574C>A | p.Ala525Asp | missense_variant | 17/27 | ||
RB1 | NM_001407166.1 | c.1574C>A | p.Ala525Asp | missense_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.1574C>A | p.Ala525Asp | missense_variant | 17/27 | 1 | NM_000321.3 | P1 | |
RB1 | ENST00000650461.1 | c.1574C>A | p.Ala525Asp | missense_variant | 17/27 | ||||
RB1 | ENST00000643064.1 | c.74C>A | p.Ala25Asp | missense_variant | 1/2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459728Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726024
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 15, 2018 | The p.A525D variant (also known as c.1574C>A), located in coding exon 17 of the RB1 gene, results from a C to A substitution at nucleotide position 1574. The alanine at codon 525 is replaced by aspartic acid, an amino acid with dissimilar properties. This amino acid position is highly conserved on sequence alignment. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at