rs116778543
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001130438.3(SPTAN1):c.6549C>A(p.Thr2183=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000683 in 1,612,474 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0035 ( 8 hom., cov: 33)
Exomes 𝑓: 0.00039 ( 7 hom. )
Consequence
SPTAN1
NM_001130438.3 synonymous
NM_001130438.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.617
Genes affected
SPTAN1 (HGNC:11273): (spectrin alpha, non-erythrocytic 1) Spectrins are a family of filamentous cytoskeletal proteins that function as essential scaffold proteins that stabilize the plasma membrane and organize intracellular organelles. Spectrins are composed of alpha and beta dimers that associate to form tetramers linked in a head-to-head arrangement. This gene encodes an alpha spectrin that is specifically expressed in nonerythrocytic cells. The encoded protein has been implicated in other cellular functions including DNA repair and cell cycle regulation. Mutations in this gene are the cause of early infantile epileptic encephalopathy-5. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 9-128626660-C-A is Benign according to our data. Variant chr9-128626660-C-A is described in ClinVar as [Benign]. Clinvar id is 139310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128626660-C-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.617 with no splicing effect.
BS2
?
High AC in GnomAd4 at 535 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTAN1 | NM_001130438.3 | c.6549C>A | p.Thr2183= | synonymous_variant | 49/57 | ENST00000372739.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTAN1 | ENST00000372739.7 | c.6549C>A | p.Thr2183= | synonymous_variant | 49/57 | 1 | NM_001130438.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00352 AC: 536AN: 152158Hom.: 8 Cov.: 33
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GnomAD3 exomes AF: 0.000970 AC: 239AN: 246304Hom.: 2 AF XY: 0.000704 AC XY: 94AN XY: 133526
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GnomAD4 exome AF: 0.000388 AC: 567AN: 1460200Hom.: 7 Cov.: 37 AF XY: 0.000336 AC XY: 244AN XY: 726298
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GnomAD4 genome ? AF: 0.00351 AC: 535AN: 152274Hom.: 8 Cov.: 33 AF XY: 0.00322 AC XY: 240AN XY: 74454
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 27, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 02, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | SPTAN1: BP4, BP7, BS1, BS2 - |
Developmental and epileptic encephalopathy, 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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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