rs34980264
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_000518.5(HBB):c.421G>A(p.Ala141Thr) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic,other (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A141D) has been classified as Uncertain significance.
Frequency
Consequence
NM_000518.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBB | NM_000518.5 | c.421G>A | p.Ala141Thr | missense_variant | 3/3 | ENST00000335295.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBB | ENST00000335295.4 | c.421G>A | p.Ala141Thr | missense_variant | 3/3 | 1 | NM_000518.5 | P1 | |
HBB | ENST00000647020.1 | c.421G>A | p.Ala141Thr | missense_variant | 3/3 | P1 | |||
HBB | ENST00000633227.1 | c.*237G>A | 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
Erythrocytosis, familial, 6 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 1984 | - - |
HEMOGLOBIN SAINT JACQUES 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