rs796053322
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP6
The NM_001130438.3(SPTAN1):c.6308A>G(p.Lys2103Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,070 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: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
SPTAN1
NM_001130438.3 missense
NM_001130438.3 missense
Scores
3
8
8
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, SPTAN1
BP6
?
Variant 9-128626419-A-G is Benign according to our data. Variant chr9-128626419-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 207350.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTAN1 | NM_001130438.3 | c.6308A>G | p.Lys2103Arg | missense_variant | 49/57 | ENST00000372739.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTAN1 | ENST00000372739.7 | c.6308A>G | p.Lys2103Arg | missense_variant | 49/57 | 1 | NM_001130438.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
3
AN:
152204
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250840Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135604
GnomAD3 exomes
AF:
AC:
1
AN:
250840
Hom.:
AF XY:
AC XY:
1
AN XY:
135604
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461866Hom.: 0 Cov.: 37 AF XY: 0.0000248 AC XY: 18AN XY: 727236
GnomAD4 exome
AF:
AC:
49
AN:
1461866
Hom.:
Cov.:
37
AF XY:
AC XY:
18
AN XY:
727236
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74360
GnomAD4 genome
?
AF:
AC:
3
AN:
152204
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74360
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 31, 2012 | p.Lys2103Arg (AAA>AGA):c.6308 A>G in exon 49 of the SPTAN1 gene (NM_001130438.1) The Lys2103Arg missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Lys2013Arg in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. This amino acid substitution is conservative, as both Arginine and Lysine are positively charged amino acids. Lys2103Arg alters a highly conserved position in the 22nd spectrin repeat of the protein, and multiple in silico algorithms predict it may be damaging to protein structure/function. However, previously reported pathogenic mutations in SPTAN1 are in frame deletions or duplications located within the last spectrin repeat of the protein (Saitsu et al., 2010). Therefore, based on the currently available information, it is unclear whether Lys2103Arg is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). - |
Developmental and epileptic encephalopathy, 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;.;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;N;.;.
REVEL
Benign
Sift
Benign
T;.;T;.;.
Sift4G
Benign
T;T;T;T;T
Polyphen
P;.;D;D;.
Vest4
MutPred
Loss of ubiquitination at K2098 (P = 0.0233);.;.;.;.;
MVP
MPC
1.7
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