rs35850071
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000558.5(HBA1):c.11C>T(p.Ser4Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as other (no stars).
Frequency
Genomes: not found (cov: 28)
Consequence
HBA1
NM_000558.5 missense
NM_000558.5 missense
Scores
6
9
3
Clinical Significance
Conservation
PhyloP100: 3.85
Genes affected
HBA1 (HGNC:4823): (hemoglobin subunit alpha 1) The human alpha globin gene cluster located on chromosome 16 spans about 30 kb and includes seven loci: 5'- zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 - alpha-1 - theta - 3'. The alpha-2 (HBA2) and alpha-1 (HBA1) coding sequences are identical. These genes differ slightly over the 5' untranslated regions and the introns, but they differ significantly over the 3' untranslated regions. Two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin; alpha chains combine with delta chains to constitute HbA-2, which with HbF (fetal hemoglobin) makes up the remaining 3% of adult hemoglobin. Alpha thalassemias result from deletions of each of the alpha genes as well as deletions of both HBA2 and HBA1; some nondeletion alpha thalassemias have also been reported. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
?
In a modified_residue Phosphoserine (size 0) in uniprot entity HBA_HUMAN
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBA1 | NM_000558.5 | c.11C>T | p.Ser4Phe | missense_variant | 1/3 | ENST00000320868.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBA1 | ENST00000320868.9 | c.11C>T | p.Ser4Phe | missense_variant | 1/3 | 1 | NM_000558.5 | P1 | |
HBA1 | ENST00000472694.1 | n.30C>T | non_coding_transcript_exon_variant | 1/2 | 1 | ||||
HBA1 | ENST00000397797.1 | c.-37C>T | 5_prime_UTR_variant | 1/3 | 2 | ||||
HBA1 | ENST00000487791.1 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 28
GnomAD3 genomes
?
Cov.:
28
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 28
GnomAD4 genome
?
Cov.:
28
ClinVar
Significance: other
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
HEMOGLOBIN DOUALA Other:1
other, no assertion criteria provided | literature only | OMIM | Jul 20, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Pathogenic
D
Vest4
MutPred
Loss of disorder (P = 0.0123);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at