rs779091056
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_006946.4(SPTBN2):c.3738C>T(p.Ala1246=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
SPTBN2
NM_006946.4 synonymous
NM_006946.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.64
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 Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 11-66699444-G-A is Benign according to our data. Variant chr11-66699444-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 586480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-5.64 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTBN2 | NM_006946.4 | c.3738C>T | p.Ala1246= | synonymous_variant | 18/38 | ENST00000533211.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTBN2 | ENST00000533211.6 | c.3738C>T | p.Ala1246= | synonymous_variant | 18/38 | 5 | NM_006946.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152008Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251480Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135920
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GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727244
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152008Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74232
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 11, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 20, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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