rs753345594
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_020191.4(MRPS22):c.605G>A(p.Arg202His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,996 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_020191.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MRPS22 | NM_020191.4 | c.605G>A | p.Arg202His | missense_variant | Exon 4 of 8 | ENST00000680020.1 | NP_064576.1 | |
MRPS22 | NM_001363893.1 | c.602G>A | p.Arg201His | missense_variant | Exon 4 of 8 | NP_001350822.1 | ||
MRPS22 | NM_001363857.1 | c.482G>A | p.Arg161His | missense_variant | Exon 4 of 8 | NP_001350786.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251424Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135884
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461836Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727220
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74348
ClinVar
Submissions by phenotype
Ovarian dysgenesis 7 Pathogenic:1
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46 XX gonadal dysgenesis Pathogenic:1
Four individuals from two independent consanguineous families with 46,XX gonadal dysgenesis were found to be homozygous for nonsynonymous variants in MRPS22. The unaffected parents and siblings were not homozygous for these mutations. In one of the consanguineous families, the region containing MRPS22 was the only region of homozygosity that segregated with the disease and the variant in MRPS22 was the only nonsynonymous variant in this interval. Additional support for the clinical significance comes from studies in Drosophila that demonstrate mRpS22 is required for fertility and germ cell development. -
Muscular dystrophy, adult-onset, with leukoencephalopathy Uncertain:1
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not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at