rs144289764
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_001130438.3(SPTAN1):āc.6488A>Gā(p.Lys2163Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,613,926 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000092 ( 0 hom., cov: 33)
Exomes š: 0.00011 ( 0 hom. )
Consequence
SPTAN1
NM_001130438.3 missense
NM_001130438.3 missense
Scores
4
10
5
Clinical Significance
Conservation
PhyloP100: 8.95
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 Likely_benign. Variant got -4 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, SPTAN1
BP6
?
Variant 9-128626599-A-G is Benign according to our data. Variant chr9-128626599-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 207354.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=3, Uncertain_significance=1}.
BS2
?
High AC in GnomAd4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTAN1 | NM_001130438.3 | c.6488A>G | p.Lys2163Arg | missense_variant | 49/57 | ENST00000372739.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTAN1 | ENST00000372739.7 | c.6488A>G | p.Lys2163Arg | missense_variant | 49/57 | 1 | NM_001130438.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152140Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000108 AC: 27AN: 250928Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135700
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GnomAD4 exome AF: 0.000107 AC: 157AN: 1461786Hom.: 0 Cov.: 37 AF XY: 0.000102 AC XY: 74AN XY: 727184
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GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152140Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74330
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 5 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jan 01, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 30, 2016 | The p.K2163R variant (also known as c.6488A>G), located in coding exon 48 of the SPTAN1 gene, results from an A to G substitution at nucleotide position 6488. The lysine at codon 2163 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 29, 2017 | 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. - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 14, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | SPTAN1: PP2, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;N;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;D;.;.
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;.;D;D;.
Vest4
MVP
MPC
1.6
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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