rs201138266
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_014845.6(FIG4):āc.2154A>Gā(p.Pro718=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,613,270 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: š 0.000046 ( 0 hom., cov: 33)
Exomes š: 0.00011 ( 0 hom. )
Consequence
FIG4
NM_014845.6 synonymous
NM_014845.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0750
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 -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 6-109789651-A-G is Benign according to our data. Variant chr6-109789651-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 476855.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.075 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FIG4 | NM_014845.6 | c.2154A>G | p.Pro718= | synonymous_variant | 19/23 | ENST00000230124.8 | |
FIG4 | XM_011536281.4 | c.2091A>G | p.Pro697= | synonymous_variant | 19/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FIG4 | ENST00000230124.8 | c.2154A>G | p.Pro718= | synonymous_variant | 19/23 | 1 | NM_014845.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152254Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000955 AC: 24AN: 251378Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135864
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GnomAD4 exome AF: 0.000111 AC: 162AN: 1461016Hom.: 0 Cov.: 30 AF XY: 0.000107 AC XY: 78AN XY: 726868
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74394
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2016 | - - |
Charcot-Marie-Tooth disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Charcot-Marie-Tooth disease type 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at