rs76180538
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001079802.2(FKTN):c.910+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,613,382 control chromosomes in the GnomAD database, including 164 homozygotes. 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 0.0085 ( 12 hom., cov: 32)
Exomes 𝑓: 0.011 ( 152 hom. )
Consequence
FKTN
NM_001079802.2 intron
NM_001079802.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0120
Genes affected
FKTN (HGNC:3622): (fukutin) The protein encoded by this gene is a putative transmembrane protein that is localized to the cis-Golgi compartment, where it may be involved in the glycosylation of alpha-dystroglycan in skeletal muscle. The encoded protein is thought to be a glycosyltransferase and could play a role in brain development. Defects in this gene are a cause of Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), limb-girdle muscular dystrophy type 2M (LGMD2M), and dilated cardiomyopathy type 1X (CMD1X). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 9-105615421-G-A is Benign according to our data. Variant chr9-105615421-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 93525.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=5, Uncertain_significance=1}. Variant chr9-105615421-G-A is described in Lovd as [Benign]. Variant chr9-105615421-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00849 (1293/152248) while in subpopulation SAS AF= 0.0201 (97/4824). AF 95% confidence interval is 0.0169. There are 12 homozygotes in gnomad4. There are 656 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 12 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FKTN | NM_001079802.2 | c.910+14G>A | intron_variant | ENST00000357998.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKTN | ENST00000357998.10 | c.910+14G>A | intron_variant | 5 | NM_001079802.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00850 AC: 1293AN: 152130Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.0113 AC: 2833AN: 251448Hom.: 29 AF XY: 0.0126 AC XY: 1710AN XY: 135896
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GnomAD4 exome AF: 0.0105 AC: 15406AN: 1461134Hom.: 152 Cov.: 31 AF XY: 0.0112 AC XY: 8140AN XY: 726934
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GnomAD4 genome ? AF: 0.00849 AC: 1293AN: 152248Hom.: 12 Cov.: 32 AF XY: 0.00881 AC XY: 656AN XY: 74434
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:11
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Benign:6
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 19, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 21, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 29, 2012 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
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 | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 26, 2023 | - - |
Dilated cardiomyopathy 1X Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 16, 2015 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Walker-Warburg congenital muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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Name
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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