rs775468466
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_003919.3(SGCE):āc.856C>Gā(p.Gln286Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,459,890 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 Uncertain significance (ā ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.000011 ( 0 hom. )
Consequence
SGCE
NM_003919.3 missense
NM_003919.3 missense
Scores
3
2
8
Clinical Significance
Conservation
PhyloP100: 6.92
Genes affected
SGCE (HGNC:10808): (sarcoglycan epsilon) This gene encodes the epsilon member of the sarcoglycan family. Sarcoglycans are transmembrane proteins that are components of the dystrophin-glycoprotein complex, which link the actin cytoskeleton to the extracellular matrix. Unlike other family members which are predominantly expressed in striated muscle, the epsilon sarcoglycan is more broadly expressed. Mutations in this gene are associated with myoclonus-dystonia syndrome. This gene is imprinted, with preferential expression from the paternal allele. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A pseudogene associated with this gene is located on chromosome 2. [provided by RefSeq, Oct 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.29663482).
BS2
?
High AC in GnomAdExome4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCE | NM_003919.3 | c.856C>G | p.Gln286Glu | missense_variant | 7/11 | ENST00000648936.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCE | ENST00000648936.2 | c.856C>G | p.Gln286Glu | missense_variant | 7/11 | NM_003919.3 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249188Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134668
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000110 AC: 16AN: 1459890Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4AN XY: 726154
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
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32
ExAC
?
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1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Myoclonic dystonia 11 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 12, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 13, 2018 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SGCE-related disease. This variant is present in population databases (rs775468466, ExAC 0.002%). This sequence change replaces glutamine with glutamic acid at codon 286 of the SGCE protein (p.Gln286Glu). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and glutamic acid. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Benign
T
Polyphen
0.037, 0.18, 0.069, 0.47
.;B;B;.;B;.;.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;P;.;.;.
Vest4
0.25, 0.24, 0.28, 0.27, 0.28
MutPred
0.43
.;.;.;.;.;Loss of sheet (P = 0.1158);.;.;.;.;.;.;.;.;.;Loss of sheet (P = 0.1158);.;.;.;.;Loss of sheet (P = 0.1158);.;.;.;.;.;.;Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;.;.;Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;.;
MVP
0.84
MPC
0.21
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at