6-18121516-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_198586.3(NHLRC1):c.1091C>A(p.Ser364*) 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 (★).
Frequency
Consequence
NM_198586.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NHLRC1 | NM_198586.3 | c.1091C>A | p.Ser364* | stop_gained | Exon 1 of 1 | ENST00000340650.6 | NP_940988.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Lafora disease Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the NHLRC1 protein. Other variant(s) that disrupt this region (Val367Trpfs*21) have been determined to be pathogenic (PMID: 12958597). This variant is also known as p.V367fs20 in the literature. This suggests that variants that disrupt this region of the protein are likely to be causative of disease. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has been observed in individual(s) with progressive myoclonic epilepsy (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the NHLRC1 gene (p.Ser364*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 32 amino acids of the NHLRC1 protein. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at