rs201576638
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_012213.3(MLYCD):c.1175G>A(p.Arg392Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. R392W) has been classified as Uncertain significance.
Frequency
Consequence
NM_012213.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MLYCD | NM_012213.3 | c.1175G>A | p.Arg392Gln | missense_variant | 5/5 | ENST00000262430.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MLYCD | ENST00000262430.6 | c.1175G>A | p.Arg392Gln | missense_variant | 5/5 | 1 | NM_012213.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000802 AC: 20AN: 249240Hom.: 0 AF XY: 0.0000887 AC XY: 12AN XY: 135244
GnomAD4 exome AF: 0.000166 AC: 242AN: 1461730Hom.: 0 Cov.: 30 AF XY: 0.000157 AC XY: 114AN XY: 727150
GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15AN XY: 74368
ClinVar
Submissions by phenotype
Deficiency of malonyl-CoA decarboxylase Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 392 of the MLYCD protein (p.Arg392Gln). This variant is present in population databases (rs201576638, gnomAD 0.02%). 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: 567925). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2021 | The c.1175G>A (p.R392Q) alteration is located in exon 5 (coding exon 5) of the MLYCD gene. This alteration results from a G to A substitution at nucleotide position 1175, causing the arginine (R) at amino acid position 392 to be replaced by a glutamine (Q). 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