rs1555721549
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_020971.3(SPTBN4):c.7453delG(p.Ala2485fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
SPTBN4
NM_020971.3 frameshift
NM_020971.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.526
Genes affected
SPTBN4 (HGNC:14896): (spectrin beta, non-erythrocytic 4) Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. This gene is one member of a family of beta-spectrin genes. The encoded protein localizes to the nuclear matrix, PML nuclear bodies, and cytoplasmic vesicles. A highly similar gene in the mouse is required for localization of specific membrane proteins in polarized regions of neurons. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-40572150-TG-T is Pathogenic according to our data. Variant chr19-40572150-TG-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 559549.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-40572150-TG-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPTBN4 | NM_020971.3 | c.7453delG | p.Ala2485fs | frameshift_variant | 34/36 | ENST00000598249.6 | NP_066022.2 | |
SPTBN4 | XM_017027049.2 | c.7453delG | p.Ala2485fs | frameshift_variant | 34/36 | XP_016882538.1 | ||
SPTBN4 | XM_017027050.2 | c.7111delG | p.Ala2371fs | frameshift_variant | 32/34 | XP_016882539.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 05, 2018 | - - |
Neurodevelopmental disorder with hypotonia, neuropathy, and deafness Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 13, 2018 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at