Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2_SupportingPM5PP3PP5_Moderate
The NM_000016.6(ACADM):c.985A>C(p.Lys329Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K329E) has been classified as Likely pathogenic.
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_000016.6
PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 32.
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr1-75761161-A-G is described in ClinVar as [Conflicting_interpretations_of_pathogenicity]. Clinvar id is 3586. Status of the report is criteria_provided_conflicting_interpretations, 1 stars. We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=31, Likely_pathogenic=2, Uncertain_significance=1}.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.809
PP5
?
Variant 1-75761161-A-C is Pathogenic according to our data. Variant chr1-75761161-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 226057. Status of the report is criteria_provided_single_submitter, 1 stars.