GeneBe

rs763945497

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006946.4(SPTBN2):​c.3332G>T​(p.Arg1111Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,786 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: 6.9e-7 ( 0 hom. )

Consequence

SPTBN2
NM_006946.4 missense

Scores

1
6
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.63
Variant links:
Genes affected
SPTBN2 (HGNC:11276): (spectrin beta, non-erythrocytic 2) Spectrins are principle components of a cell's membrane-cytoskeleton and are composed of two alpha and two beta spectrin subunits. The protein encoded by this gene (SPTBN2), is called spectrin beta non-erythrocytic 2 or beta-III spectrin. It is related to, but distinct from, the beta-II spectrin gene which is also known as spectrin beta non-erythrocytic 1 (SPTBN1). SPTBN2 regulates the glutamate signaling pathway by stabilizing the glutamate transporter EAAT4 at the surface of the plasma membrane. Mutations in this gene cause a form of spinocerebellar ataxia, SCA5, that is characterized by neurodegeneration, progressive locomotor incoordination, dysarthria, and uncoordinated eye movements. [provided by RefSeq, Dec 2009]

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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;
BP4
Computational evidence support a benign effect (MetaRNN=0.33430648).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPTBN2NM_006946.4 linkc.3332G>T p.Arg1111Leu missense_variant Exon 17 of 38 ENST00000533211.6 NP_008877.2 O15020-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPTBN2ENST00000533211.6 linkc.3332G>T p.Arg1111Leu missense_variant Exon 17 of 38 5 NM_006946.4 ENSP00000432568.1 O15020-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.90e-7
AC:
1
AN:
1449786
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
721772
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.065
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
T;T;.
Eigen
Benign
0.023
Eigen_PC
Benign
0.098
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.72
.;T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.33
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.94
L;L;L
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-4.5
D;D;D
REVEL
Benign
0.15
Sift
Uncertain
0.019
D;D;D
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
0.52
P;P;.
Vest4
0.30
MutPred
0.59
Loss of methylation at R1111 (P = 0.0273);Loss of methylation at R1111 (P = 0.0273);Loss of methylation at R1111 (P = 0.0273);
MVP
0.46
MPC
1.1
ClinPred
0.98
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.40
gMVP
0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-66468238; API