chr3-139348224-G-A
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_020191.4(MRPS22):c.404G>A(p.Arg135Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,992 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 (★).
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)
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MRPS22 | NM_020191.4 | c.404G>A | p.Arg135Gln | missense_variant | Exon 3 of 8 | ENST00000680020.1 | NP_064576.1 | |
MRPS22 | NM_001363893.1 | c.401G>A | p.Arg134Gln | missense_variant | Exon 3 of 8 | NP_001350822.1 | ||
MRPS22 | NM_001363857.1 | c.281G>A | p.Arg94Gln | missense_variant | Exon 3 of 8 | NP_001350786.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33 show subpopulations
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461784Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727204 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74362 show subpopulations
ClinVar
Submissions by phenotype
Premature ovarian failure Uncertain:2
This variant was identified as homozygous in a female individual with hypergonadotropic hypogonadism. -
This variant was identified as homozygous in a female with primary ovarian insufficiency, with reduced bone age, small uterus, and ovaries that could not be visualized by pelvic ultrasound. Karyotype was 46,XX. The variant was not identified in control databases including gnomAD, nor a population-specific (Turkish) database of > 1000 exomes. -
Ovarian dysgenesis 7 Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at