chr13-48367518-G-T
Variant summary
Our verdict is Pathogenic. The variant received 13 ACMG points: 13P and 0B. PVS1PM2PP3PP5_Moderate
The NM_000321.3(RB1):c.964G>T(p.Glu322*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000321.3 stop_gained
Scores
Clinical Significance
Conservation
Publications
- hereditary retinoblastomaInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
- retinoblastomaInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- melanomaInheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
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ACMG classification
Our verdict: Pathogenic. The variant received 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.964G>T | p.Glu322* | stop_gained | Exon 10 of 27 | ENST00000267163.6 | NP_000312.2 | |
RB1 | NM_001407165.1 | c.964G>T | p.Glu322* | stop_gained | Exon 10 of 27 | NP_001394094.1 | ||
RB1 | NM_001407166.1 | c.964G>T | p.Glu322* | stop_gained | Exon 10 of 17 | NP_001394095.1 | ||
LOC112268118 | XR_002957522.2 | n.122-2542C>A | intron_variant | Intron 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1451638Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 721854
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
The p.E322* pathogenic mutation (also known as c.964G>T), located in coding exon 10 of the RB1 gene, results from a G to T substitution at nucleotide position 964. This changes the amino acid from a glutamic acid to a stop codon within coding exon 10. This mutation was detected in two relatives diagnosed with retinoblastoma (Taylor M et al. Hum. Mutat. 2007 Mar;28(3):284-93). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at