rs1553691918
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_021971.4(GMPPB):c.458_459del(p.Thr153ArgfsTer17) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000137 in 1,461,496 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. T153T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_021971.4 frameshift
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 |
---|---|---|---|---|---|---|---|
GMPPB | NM_021971.4 | c.458_459del | p.Thr153ArgfsTer17 | frameshift_variant | 5/9 | ENST00000308388.7 | |
GMPPB | NM_013334.4 | c.458_459del | p.Thr153ArgfsTer17 | frameshift_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GMPPB | ENST00000308388.7 | c.458_459del | p.Thr153ArgfsTer17 | frameshift_variant | 5/9 | 1 | NM_021971.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461496Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727024
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14;C3809221:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14;C4518000:Autosomal recessive limb-girdle muscular dystrophy type 2T Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 05, 2017 | This sequence change creates a premature translational stop signal (p.Thr153Argfs*17) in the GMPPB gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a GMPPB-related disease. Loss-of-function variants in GMPPB are known to be pathogenic  (PMID: 23768512). For these reasons, this variant has been classified as Pathogenic. - |
Abnormality of the musculature Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Kariminejad - Najmabadi Pathology & Genetics Center | Jul 10, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at