rs1189469219
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_003919.3(SGCE):c.783delA(p.Lys261AsnfsTer28) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. K261K) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SGCE
NM_003919.3 frameshift
NM_003919.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.150
Publications
0 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 12 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 7-94603331-AT-A is Pathogenic according to our data. Variant chr7-94603331-AT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 2571286.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_003919.3. 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 | MANE Select | c.783delA | p.Lys261AsnfsTer28 | frameshift | Exon 6 of 11 | NP_003910.1 | A0A0S2Z4P5 | ||
| SGCE | c.891delA | p.Lys297AsnfsTer28 | frameshift | Exon 7 of 12 | NP_001333642.1 | A0A2R8YGQ3 | |||
| SGCE | c.891delA | p.Lys297AsnfsTer28 | frameshift | Exon 7 of 11 | NP_001333644.1 | A0A2R8Y5J3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SGCE | MANE Select | c.783delA | p.Lys261AsnfsTer28 | frameshift | Exon 6 of 11 | ENSP00000497130.1 | O43556-1 | ||
| SGCE | TSL:1 | c.762delA | p.Lys254AsnfsTer28 | frameshift | Exon 6 of 11 | ENSP00000397536.3 | A0A2U3TZN7 | ||
| SGCE | TSL:1 | c.783delA | p.Lys261AsnfsTer28 | frameshift | Exon 6 of 10 | ENSP00000388734.1 | C9JR67 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000401 AC: 1AN: 249238 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
249238
AF XY:
Gnomad AFR exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460586Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726530 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1460586
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
726530
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33440
American (AMR)
AF:
AC:
0
AN:
44602
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26096
East Asian (EAS)
AF:
AC:
0
AN:
39614
South Asian (SAS)
AF:
AC:
0
AN:
86088
European-Finnish (FIN)
AF:
AC:
0
AN:
53360
Middle Eastern (MID)
AF:
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111294
Other (OTH)
AF:
AC:
0
AN:
60336
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.550
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
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Prediction
PhyloP100
Splicing
Name
Calibrated prediction
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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
Publications
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