3-183034014-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020166.5(MCCC1):c.1658T>A(p.Met553Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,688 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M553V) has been classified as Uncertain significance.
Frequency
Consequence
NM_020166.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCCC1 | NM_020166.5 | c.1658T>A | p.Met553Lys | missense_variant | 14/19 | ENST00000265594.9 | |
LOC124906309 | XR_007096188.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCCC1 | ENST00000265594.9 | c.1658T>A | p.Met553Lys | missense_variant | 14/19 | 1 | NM_020166.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251082Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135758
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1457688Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 725454
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
3-methylcrotonyl-CoA carboxylase 1 deficiency Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 24, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 07, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 553 of the MCCC1 protein (p.Met553Lys). This variant is present in population databases (rs774055789, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of MCCC1-related conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 542945). 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 not expected to disrupt MCCC1 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at