rs1555194630
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_145064.3(STAC3):c.383_399del(p.His128LeufsTer20) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,954 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: 31)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
STAC3
NM_145064.3 frameshift
NM_145064.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.34
Genes affected
STAC3 (HGNC:28423): (SH3 and cysteine rich domain 3) The protein encoded by this gene is a component of the excitation-contraction coupling machinery of muscles. This protein is a member of the Stac gene family and contains an N-terminal cysteine-rich domain and two SH3 domains. Mutations in this gene are a cause of Native American myopathy. [provided by RefSeq, Nov 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 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 12-57248738-AGGACTGACAGTGTTCAT-A is Pathogenic according to our data. Variant chr12-57248738-AGGACTGACAGTGTTCAT-A is described in ClinVar as [Pathogenic]. Clinvar id is 465659.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STAC3 | NM_145064.3 | c.383_399del | p.His128LeufsTer20 | frameshift_variant | 4/12 | ENST00000332782.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STAC3 | ENST00000332782.7 | c.383_399del | p.His128LeufsTer20 | frameshift_variant | 4/12 | 2 | NM_145064.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461790Hom.: 0 AF XY: 0.0000179 AC XY: 13AN XY: 727192
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74330
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Bailey-Bloch congenital myopathy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2021 | ClinVar contains an entry for this variant (Variation ID: 465659). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with STAC3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His128Leufs*20) in the STAC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in STAC3 are known to be pathogenic (PMID: 28411587, 28777491). - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at