11-5225617-A-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_000518.5(HBB):c.425T>G(p.Leu142Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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 Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L142V) has been classified as Uncertain significance.
Frequency
Consequence
NM_000518.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBB | NM_000518.5 | c.425T>G | p.Leu142Arg | missense_variant | 3/3 | ENST00000335295.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBB | ENST00000335295.4 | c.425T>G | p.Leu142Arg | missense_variant | 3/3 | 1 | NM_000518.5 | P1 | |
HBB | ENST00000647020.1 | c.425T>G | p.Leu142Arg | missense_variant | 3/3 | P1 | |||
HBB | ENST00000633227.1 | c.*241T>G | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 3 | ||||
HBB | ENST00000475226.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Sep 20, 2023 | The HBB c.425T>G (p.Leu142Arg) variant has been reported in the published literature in individuals with hemolytic anemia and is known as Hb Olmsted (PMID: 5780360 (1969), 8579053 (1996)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, we are unable to determine the clinical significance of this variant. - |
HEMOGLOBIN OLMSTED Other:1
other, no assertion criteria provided | literature only | OMIM | Dec 12, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at