rs794727794
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001346713.2(SGCE):c.879_880delAT(p.Cys294fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,458 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SGCE
NM_001346713.2 frameshift
NM_001346713.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.95
Publications
3 publications found
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]
CASD1 (HGNC:16014): (CAS1 domain containing 1) Enables N-acetylneuraminate 7-O(or 9-O)-acetyltransferase activity. Involved in carbohydrate metabolic process. Is integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 7-94603342-CAT-C is Pathogenic according to our data. Variant chr7-94603342-CAT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 198162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001346713.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SGCE | NM_003919.3 | MANE Select | c.771_772delAT | p.Cys258fs | frameshift | Exon 6 of 11 | NP_003910.1 | ||
| SGCE | NM_001346713.2 | c.879_880delAT | p.Cys294fs | frameshift | Exon 7 of 12 | NP_001333642.1 | |||
| SGCE | NM_001346715.2 | c.879_880delAT | p.Cys294fs | frameshift | Exon 7 of 11 | NP_001333644.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SGCE | ENST00000648936.2 | MANE Select | c.771_772delAT | p.Cys258fs | frameshift | Exon 6 of 11 | ENSP00000497130.1 | ||
| SGCE | ENST00000428696.7 | TSL:1 | c.750_751delAT | p.Cys251fs | frameshift | Exon 6 of 11 | ENSP00000397536.3 | ||
| SGCE | ENST00000447873.6 | TSL:1 | c.771_772delAT | p.Cys258fs | frameshift | Exon 6 of 10 | ENSP00000388734.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152148
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460310Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726450 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1460310
Hom.:
AF XY:
AC XY:
1
AN XY:
726450
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33436
American (AMR)
AF:
AC:
0
AN:
44614
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26104
East Asian (EAS)
AF:
AC:
0
AN:
39604
South Asian (SAS)
AF:
AC:
0
AN:
86110
European-Finnish (FIN)
AF:
AC:
0
AN:
53364
Middle Eastern (MID)
AF:
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1110992
Other (OTH)
AF:
AC:
0
AN:
60328
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
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>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74324 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152148
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74324
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41432
American (AMR)
AF:
AC:
0
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5200
South Asian (SAS)
AF:
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
AC:
0
AN:
10608
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68008
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
5
-
-
not provided (5)
3
-
-
Myoclonic dystonia 11 (3)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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