Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP3BP4_ModerateBP6_Moderate
The NM_001128918.3(MARK3):āc.886G>Cā(p.Gly296Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,613,688 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 Likely benign (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G296S) has been classified as Uncertain significance.
MARK3 (HGNC:6897): (microtubule affinity regulating kinase 3) The protein encoded by this gene is activated by phosphorylation and in turn is involved in the phosphorylation of tau proteins MAP2 and MAP4. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, Cadd, Dann, Eigen, FATHMM_MKL, phyloP100way_vertebrate, PrimateAI, PROVEAN [when max_spliceai, MetaRNN, MutationAssessor, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.08514944).
BP6
Variant 14-103466080-G-C is Benign according to our data. Variant chr14-103466080-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3041077.Status of the report is criteria_provided_single_submitter, 1 stars.
Likely benign, criteria provided, single submitter
clinical testing
PreventionGenetics, part of Exact Sciences
Sep 17, 2019
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -