11-66701629-G-C

Variant summary

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

The NM_006946.4(SPTBN2):​c.2771C>G​(p.Pro924Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,878 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: 31)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

SPTBN2
NM_006946.4 missense

Scores

1
7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.28
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=0.26674104).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPTBN2NM_006946.4 linkc.2771C>G p.Pro924Arg missense_variant Exon 16 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.2771C>G p.Pro924Arg missense_variant Exon 16 of 38 5 NM_006946.4 ENSP00000432568.1 O15020-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461878
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
727242
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
T;T;.
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.74
.;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
0.17
N;N;N
PrimateAI
Benign
0.33
T
PROVEAN
Pathogenic
-6.7
D;D;D
REVEL
Benign
0.17
Sift
Uncertain
0.024
D;D;D
Sift4G
Uncertain
0.045
D;D;D
Polyphen
0.58
P;P;.
Vest4
0.34
MutPred
0.54
Gain of MoRF binding (P = 3e-04);Gain of MoRF binding (P = 3e-04);Gain of MoRF binding (P = 3e-04);
MVP
0.38
MPC
0.44
ClinPred
0.56
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.30
gMVP
0.27

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: chr11-66469100; API