9-128594296-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001130438.3(SPTAN1):​c.3337G>T​(p.Ala1113Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPTAN1
NM_001130438.3 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.98
Variant links:
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SPTAN1. . Gene score misZ 5.523 (greater than the threshold 3.09). Trascript score misZ 7.9287 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy, 5, developmental and epileptic encephalopathy, West syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.12118119).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPTAN1NM_001130438.3 linkuse as main transcriptc.3337G>T p.Ala1113Ser missense_variant 24/57 ENST00000372739.7 NP_001123910.1 Q13813-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SPTAN1ENST00000372739.7 linkuse as main transcriptc.3337G>T p.Ala1113Ser missense_variant 24/571 NM_001130438.3 ENSP00000361824.4 Q13813-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251432
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461894
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.15
T;.;.;.;.
Eigen
Benign
-0.081
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.87
D;D;D;D;D
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.12
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.42
N;.;N;.;.
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.0
N;.;N;.;.
REVEL
Benign
0.041
Sift
Benign
0.29
T;.;T;.;.
Sift4G
Benign
0.41
T;T;T;T;T
Polyphen
0.0030
B;.;B;B;.
Vest4
0.13
MutPred
0.44
Gain of phosphorylation at A1113 (P = 0.0714);.;Gain of phosphorylation at A1113 (P = 0.0714);.;Gain of phosphorylation at A1113 (P = 0.0714);
MVP
0.30
MPC
0.72
ClinPred
0.36
T
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.068
gMVP
0.097

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs143309753; hg19: chr9-131356575; COSMIC: COSV63987479; COSMIC: COSV63987479; API