rs727504009
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_022132.5(MCCC2):c.478G>A(p.Ala160Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,018 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A160G) has been classified as Uncertain significance.
Frequency
Consequence
NM_022132.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCCC2 | NM_022132.5 | c.478G>A | p.Ala160Thr | missense_variant | 5/17 | ENST00000340941.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCCC2 | ENST00000340941.11 | c.478G>A | p.Ala160Thr | missense_variant | 5/17 | 1 | NM_022132.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251476Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135912
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727234
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74330
ClinVar
Submissions by phenotype
3-methylcrotonyl-CoA carboxylase 2 deficiency Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 10, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 02, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 160 of the MCCC2 protein (p.Ala160Thr). This variant is present in population databases (rs727504009, gnomAD 0.003%). This missense change has been observed in individual(s) with unspecified type of inborn error of metabolism (PMID: 32778825). ClinVar contains an entry for this variant (Variation ID: 167277). 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 MCCC2 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 03, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at