rs1555370967
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_001355436.2(SPTB):c.1331_1338del(p.Leu444ProfsTer3) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
SPTB
NM_001355436.2 frameshift
NM_001355436.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.29
Genes affected
SPTB (HGNC:11274): (spectrin beta, erythrocytic) This locus encodes a member of the spectrin gene family. Spectrin proteins, along with ankyrin, play a role in cell membrane organization and stability. The protein encoded by this locus functions in stability of erythrocyte membranes, and mutations in this gene have been associated with spherocytosis type 2, hereditary elliptocytosis, and neonatal hemolytic anemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 14-64796559-GGGCCACGA-G is Pathogenic according to our data. Variant chr14-64796559-GGGCCACGA-G is described in ClinVar as [Pathogenic]. Clinvar id is 544810.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTB | NM_001355436.2 | c.1331_1338del | p.Leu444ProfsTer3 | frameshift_variant | 11/36 | ENST00000644917.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTB | ENST00000644917.1 | c.1331_1338del | p.Leu444ProfsTer3 | frameshift_variant | 11/36 | NM_001355436.2 | P1 | ||
SPTB | ENST00000389720.4 | c.1331_1338del | p.Leu444ProfsTer3 | frameshift_variant | 11/32 | 5 | |||
SPTB | ENST00000389722.7 | c.1331_1338del | p.Leu444ProfsTer3 | frameshift_variant | 10/35 | 2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spherocytosis type 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Department of Genetic, Henri Mondor Hospital, Assistance Publique des Hôpitaux de Paris | Feb 27, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at