chr6-109691451-GC-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The ENST00000230124.8(FIG4):βc.21delβ(p.Ile8SerfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,060 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β ). Synonymous variant affecting the same amino acid position (i.e. A6A) has been classified as Likely benign.
Frequency
Consequence
ENST00000230124.8 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FIG4 | NM_014845.6 | c.21del | p.Ile8SerfsTer19 | frameshift_variant | 1/23 | ENST00000230124.8 | NP_055660.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FIG4 | ENST00000230124.8 | c.21del | p.Ile8SerfsTer19 | frameshift_variant | 1/23 | 1 | NM_014845.6 | ENSP00000230124 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1432006Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 709478
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74280
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 4 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 07, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with FIG4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile8Serfs*19) in the FIG4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FIG4 are known to be pathogenic (PMID: 23623387). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at