NM_020191.4:c.404G>T
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_020191.4(MRPS22):c.404G>T(p.Arg135Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R135Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_020191.4 missense
Scores
Clinical Significance
Conservation
Publications
- mitochondrial diseaseInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- hypotonia with lactic acidemia and hyperammonemiaInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
- 46 XX gonadal dysgenesisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- ovarian dysgenesis 7Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MRPS22 | NM_020191.4 | c.404G>T | p.Arg135Leu | missense_variant | Exon 3 of 8 | ENST00000680020.1 | NP_064576.1 | |
MRPS22 | NM_001363893.1 | c.401G>T | p.Arg134Leu | missense_variant | Exon 3 of 8 | NP_001350822.1 | ||
MRPS22 | NM_001363857.1 | c.281G>T | p.Arg94Leu | missense_variant | Exon 3 of 8 | NP_001350786.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251386 AF XY: 0.00 show subpopulations
GnomAD4 exome Cov.: 31
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74362 show subpopulations
Age Distribution
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at