chr19-46756017-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6BP7BS1BS2_Supporting
The NM_024301.5(FKRP):c.567C>T(p.Pro189Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,572,228 control chromosomes in the GnomAD database, including 2 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 0.0013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00019 ( 2 hom. )
Consequence
FKRP
NM_024301.5 synonymous
NM_024301.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.801
Genes affected
FKRP (HGNC:17997): (fukutin related protein) This gene encodes a protein which is targeted to the medial Golgi apparatus and is necessary for posttranslational modification of dystroglycan. Mutations in this gene have been associated with congenital muscular dystrophy, cognitive disability, and cerebellar cysts. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 19-46756017-C-T is Benign according to our data. Variant chr19-46756017-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 261691.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2, Likely_benign=4}. Variant chr19-46756017-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.801 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00134 (204/151968) while in subpopulation AFR AF= 0.00458 (190/41492). AF 95% confidence interval is 0.00405. There are 0 homozygotes in gnomad4. There are 97 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FKRP | NM_024301.5 | c.567C>T | p.Pro189Pro | synonymous_variant | Exon 4 of 4 | ENST00000318584.10 | NP_077277.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00134 AC: 203AN: 151858Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000334 AC: 61AN: 182622Hom.: 0 AF XY: 0.000275 AC XY: 28AN XY: 101966
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GnomAD4 exome AF: 0.000192 AC: 272AN: 1420260Hom.: 2 Cov.: 32 AF XY: 0.000176 AC XY: 124AN XY: 705172
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GnomAD4 genome AF: 0.00134 AC: 204AN: 151968Hom.: 0 Cov.: 33 AF XY: 0.00131 AC XY: 97AN XY: 74306
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:7
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 18, 2020 | This variant is associated with the following publications: (PMID: 14647208) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 17, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2023 | FKRP: BP4, BP7 - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 25, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jun 17, 2024 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2I Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 24, 2019 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 05, 2019 | 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. - |
Walker-Warburg congenital muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 02, 2025 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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