rs1127771
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_014845.6(FIG4):c.2559G>A(p.Ser853=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,611,466 control chromosomes in the GnomAD database, including 144,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.36 ( 11207 hom., cov: 32)
Exomes 𝑓: 0.42 ( 133281 hom. )
Consequence
FIG4
NM_014845.6 synonymous
NM_014845.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.65
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 6-109825100-G-A is Benign according to our data. Variant chr6-109825100-G-A is described in ClinVar as [Benign]. Clinvar id is 260449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109825100-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2.65 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FIG4 | NM_014845.6 | c.2559G>A | p.Ser853= | synonymous_variant | 23/23 | ENST00000230124.8 | |
FIG4 | XM_011536281.4 | c.2496G>A | p.Ser832= | synonymous_variant | 23/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FIG4 | ENST00000230124.8 | c.2559G>A | p.Ser853= | synonymous_variant | 23/23 | 1 | NM_014845.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.359 AC: 54508AN: 151896Hom.: 11209 Cov.: 32
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GnomAD3 exomes AF: 0.439 AC: 110072AN: 250872Hom.: 25733 AF XY: 0.447 AC XY: 60563AN XY: 135596
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GnomAD4 exome AF: 0.422 AC: 615174AN: 1459452Hom.: 133281 Cov.: 35 AF XY: 0.426 AC XY: 309595AN XY: 726214
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GnomAD4 genome ? AF: 0.359 AC: 54514AN: 152014Hom.: 11207 Cov.: 32 AF XY: 0.366 AC XY: 27153AN XY: 74280
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ClinVar
Significance: Benign
Submissions summary: Benign:15
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Amyotrophic lateral sclerosis type 11 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Charcot-Marie-Tooth disease type 4J Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Yunis-Varon syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Bilateral parasagittal parieto-occipital polymicrogyria Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Charcot-Marie-Tooth disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Charcot-Marie-Tooth disease type 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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