chr4-3463346-G-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_173660.5(DOK7):c.-30G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,447,188 control chromosomes in the GnomAD database, including 8,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.076 ( 678 hom., cov: 32)
Exomes 𝑓: 0.10 ( 8138 hom. )
Consequence
DOK7
NM_173660.5 5_prime_UTR
NM_173660.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.61
Genes affected
DOK7 (HGNC:26594): (docking protein 7) The protein encoded by this gene is essential for neuromuscular synaptogenesis. The protein functions in aneural activation of muscle-specific receptor kinase, which is required for postsynaptic differentiation, and in the subsequent clustering of the acetylcholine receptor in myotubes. This protein can also induce autophosphorylation of muscle-specific receptor kinase. Mutations in this gene are a cause of familial limb-girdle myasthenia autosomal recessive, which is also known as congenital myasthenic syndrome type 1B. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 4-3463346-G-T is Benign according to our data. Variant chr4-3463346-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 262861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-3463346-G-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOK7 | NM_173660.5 | c.-30G>T | 5_prime_UTR_variant | 1/7 | ENST00000340083.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOK7 | ENST00000340083.6 | c.-30G>T | 5_prime_UTR_variant | 1/7 | 1 | NM_173660.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0759 AC: 11521AN: 151812Hom.: 677 Cov.: 32
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GnomAD3 exomes AF: 0.113 AC: 9379AN: 83258Hom.: 698 AF XY: 0.118 AC XY: 5632AN XY: 47570
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GnomAD4 exome AF: 0.105 AC: 135896AN: 1295270Hom.: 8138 Cov.: 32 AF XY: 0.108 AC XY: 68873AN XY: 637794
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GnomAD4 genome AF: 0.0759 AC: 11527AN: 151918Hom.: 678 Cov.: 32 AF XY: 0.0784 AC XY: 5820AN XY: 74246
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 20, 2016 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
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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