rs63751035
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_002087.4(GRN):c.759_760del(p.Cys253Ter) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,706 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. T251T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_002087.4 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 |
---|---|---|---|---|---|---|---|
GRN | NM_002087.4 | c.759_760del | p.Cys253Ter | frameshift_variant | 8/13 | ENST00000053867.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRN | ENST00000053867.8 | c.759_760del | p.Cys253Ter | frameshift_variant | 8/13 | 1 | NM_002087.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251158Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135752
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461706Hom.: 0 AF XY: 0.00000550 AC XY: 4AN XY: 727168
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Frontotemporal dementia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Human Genetics Group at Institute of Prion Diseases London, University College London | Feb 01, 2017 | Variant causing termination in GRN. Haploinsufficiency is a well established cause of disease in GRN - |
GRN-related frontotemporal lobar degeneration with Tdp43 inclusions Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | Jan 23, 2018 | - - |
not provided Other:1
not provided, no classification provided | literature only | VIB Department of Molecular Genetics, University of Antwerp | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at