rs374450869
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The ENST00000230124.8(FIG4):c.2376+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
FIG4
ENST00000230124.8 intron
ENST00000230124.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0670
Genes affected
FIG4 (HGNC:16873): (FIG4 phosphoinositide 5-phosphatase) The protein encoded by this gene belongs to the SAC domain-containing protein gene family. The SAC domain, approximately 400 amino acids in length and consisting of seven conserved motifs, has been shown to possess phosphoinositide phosphatase activity. The yeast homolog, Sac1p, is involved in the regulation of various phosphoinositides, and affects diverse cellular functions such as actin cytoskeleton organization, Golgi function, and maintenance of vacuole morphology. Membrane-bound phosphoinositides function as signaling molecules and play a key role in vesicle trafficking in eukaryotic cells. Mutations in this gene have been associated with Charcot-Marie-Tooth disease, type 4J. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 6-109791580-G-A is Benign according to our data. Variant chr6-109791580-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 447334.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FIG4 | NM_014845.6 | c.2376+9G>A | intron_variant | ENST00000230124.8 | NP_055660.1 | |||
FIG4 | XM_011536281.4 | c.2313+9G>A | intron_variant | XP_011534583.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FIG4 | ENST00000230124.8 | c.2376+9G>A | intron_variant | 1 | NM_014845.6 | ENSP00000230124 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152200Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000641 AC: 16AN: 249498Hom.: 0 AF XY: 0.0000740 AC XY: 10AN XY: 135094
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1460994Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 726806
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GnomAD4 genome AF: 0.000112 AC: 17AN: 152318Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74492
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 19, 2016 | - - |
Charcot-Marie-Tooth disease type 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 01, 2023 | - - |
Computational scores
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Benign
CADD
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DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at