rs398123812
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_003919.3(SGCE):c.709C>T(p.Arg237Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,460,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R237R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_003919.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCE | NM_003919.3 | c.709C>T | p.Arg237Ter | stop_gained | 6/11 | ENST00000648936.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCE | ENST00000648936.2 | c.709C>T | p.Arg237Ter | stop_gained | 6/11 | NM_003919.3 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1460956Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726790
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Knight Diagnostic Laboratories, Oregon Health and Sciences University | May 17, 2019 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2019 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 09, 2012 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 14, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23641306, 25525159, 18759336, 19117361, 18205193, 23332219, 18175340, 12391346, 33022436, 15389977, 24297365, 12821748, 31423828) - |
Myoclonic dystonia 11 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 22, 2023 | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 94384). This premature translational stop signal has been observed in individual(s) with myoclonus-dystonia (PMID: 18205193). This sequence change creates a premature translational stop signal (p.Arg237*) in the SGCE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SGCE are known to be pathogenic (PMID: 12821748, 15389977, 17853490, 24297365). - |
Pathogenic, criteria provided, single submitter | clinical testing | 3billion | - | The variant is not observed in the gnomAD v2.1.1 dataset. The variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000094384 / PMID: 18205193). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at