3-183017321-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_020166.5(MCCC1):c.1994G>A(p.Gly665Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,850 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_020166.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MCCC1 | NM_020166.5 | c.1994G>A | p.Gly665Glu | missense_variant | Exon 18 of 19 | ENST00000265594.9 | NP_064551.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251162Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135782
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461540Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727098
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152310Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74484
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1994G>A (p.G665E) alteration is located in exon 18 (coding exon 18) of the MCCC1 gene. This alteration results from a G to A substitution at nucleotide position 1994, causing the glycine (G) at amino acid position 665 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
3-methylcrotonyl-CoA carboxylase 1 deficiency Uncertain:1
This sequence change replaces glycine with glutamic acid at codon 665 of the MCCC1 protein (p.Gly665Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MCCC1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at