3-148994159-C-CT
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_004130.4(GYG1):c.26dup(p.Thr10AsnfsTer47) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,158 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. L9L) has been classified as Likely benign.
Frequency
Consequence
NM_004130.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GYG1 | NM_004130.4 | c.26dup | p.Thr10AsnfsTer47 | frameshift_variant | 2/8 | ENST00000345003.9 | |
GYG1 | NM_001184720.2 | c.26dup | p.Thr10AsnfsTer47 | frameshift_variant | 2/7 | ||
GYG1 | NM_001184721.2 | c.26dup | p.Thr10AsnfsTer47 | frameshift_variant | 2/6 | ||
GYG1 | XM_017006275.2 | c.-34-2142dup | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GYG1 | ENST00000345003.9 | c.26dup | p.Thr10AsnfsTer47 | frameshift_variant | 2/8 | 1 | NM_004130.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461158Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726920
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Glycogen storage disease XV;C4015452:Polyglucosan body myopathy type 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2023 | This sequence change creates a premature translational stop signal (p.Thr10Asnfs*47) in the GYG1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GYG1 are known to be pathogenic (PMID: 20357282, 25272951). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GYG1-related conditions. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at