rs780264754
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000023.4(SGCA):c.402C>A(p.Tyr134Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Y134Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000023.4 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCA | NM_000023.4 | c.402C>A | p.Tyr134Ter | stop_gained | 5/10 | ENST00000262018.8 | |
SGCA | NM_001135697.3 | c.402C>A | p.Tyr134Ter | stop_gained | 5/8 | ||
SGCA | NR_135553.2 | n.438C>A | non_coding_transcript_exon_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCA | ENST00000262018.8 | c.402C>A | p.Tyr134Ter | stop_gained | 5/10 | 1 | NM_000023.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1430250Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 708506
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2D Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 19, 2020 | This nonsense variant has been observed in individual(s) with limb-girdle muscular dystrophy (LGMD) (PMID: 30919934). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr134*) in the SGCA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SGCA are known to be pathogenic (PMID: 9192266). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.