rs121909818
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 8P and 1B. PM1PM2PM5PP5_ModerateBP4
The NM_000518.5(HBB):c.328G>C(p.Val110Leu) 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. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V110M) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000518.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBB | NM_000518.5 | c.328G>C | p.Val110Leu | missense_variant | 3/3 | ENST00000335295.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBB | ENST00000335295.4 | c.328G>C | p.Val110Leu | missense_variant | 3/3 | 1 | NM_000518.5 | P1 | |
HBB | ENST00000647020.1 | c.328G>C | p.Val110Leu | missense_variant | 3/3 | P1 | |||
HBB | ENST00000475226.1 | n.260G>C | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
HBB | ENST00000633227.1 | c.*144G>C | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Sep 04, 2019 | Found in at least one patient with expected phenotype for this gene. Predicted to have a tolerated effect on the protein. Assessment of experimental evidence suggests this variant results in abnormal protein function. Segregation with disease in affected and unaffected individuals from multiple families. - |
HEMOGLOBIN JOHNSTOWN 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