1-45509055-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_015506.3(MMACHC):c.689G>T(p.Arg230Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,666 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. R230P) has been classified as Uncertain significance.
Frequency
Consequence
NM_015506.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMACHC | NM_015506.3 | c.689G>T | p.Arg230Leu | missense_variant | 4/4 | ENST00000401061.9 | |
MMACHC | NM_001330540.2 | c.518G>T | p.Arg173Leu | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMACHC | ENST00000401061.9 | c.689G>T | p.Arg230Leu | missense_variant | 4/4 | 2 | NM_015506.3 | P1 | |
MMACHC | ENST00000616135.1 | c.518G>T | p.Arg173Leu | missense_variant | 4/5 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249088Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135120
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461666Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727132
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 13, 2021 | The c.689G>T (p.R230L) alteration is located in exon 4 (coding exon 4) of the MMACHC gene. This alteration results from a G to T substitution at nucleotide position 689, causing the arginine (R) at amino acid position 230 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