rs200188353
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PM5PP3PP5_Moderate
The NM_004279.3(PMPCB):c.524G>A(p.Arg175His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,814 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 Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R175C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_004279.3 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMPCB | NM_004279.3 | c.524G>A | p.Arg175His | missense_variant | 5/13 | ENST00000249269.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMPCB | ENST00000249269.9 | c.524G>A | p.Arg175His | missense_variant | 5/13 | 1 | NM_004279.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251322Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135836
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461498Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25AN XY: 727072
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152316Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74474
ClinVar
Submissions by phenotype
Multiple mitochondrial dysfunctions syndrome 6 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | Sep 23, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 03, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at