16-83912320-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_012213.3(MLYCD):c.901G>C(p.Val301Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000477 in 1,614,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_012213.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000801 AC: 20AN: 249536Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135398
GnomAD4 exome AF: 0.0000458 AC: 67AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727242
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74480
ClinVar
Submissions by phenotype
Deficiency of malonyl-CoA decarboxylase Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 301 of the MLYCD protein (p.Val301Leu). This variant is present in population databases (rs199656023, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MLYCD-related conditions. ClinVar contains an entry for this variant (Variation ID: 460447). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MLYCD protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Inborn genetic diseases Uncertain:1
The c.901G>C (p.V301L) alteration is located in exon 4 (coding exon 4) of the MLYCD gene. This alteration results from a G to C substitution at nucleotide position 901, causing the valine (V) at amino acid position 301 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at