chr22-38132922-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3PP5
The NM_003560.4(PLA2G6):c.986G>A(p.Arg329His) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,558,120 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). Synonymous variant affecting the same amino acid position (i.e. R329R) has been classified as Likely benign.
Frequency
Consequence
NM_003560.4 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 |
---|---|---|---|---|---|---|---|
PLA2G6 | NM_003560.4 | c.986G>A | p.Arg329His | missense_variant | 7/17 | ENST00000332509.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLA2G6 | ENST00000332509.8 | c.986G>A | p.Arg329His | missense_variant | 7/17 | 1 | NM_003560.4 | P3 | |
ENST00000624072.1 | n.2707C>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000241 AC: 4AN: 166202Hom.: 0 AF XY: 0.0000227 AC XY: 2AN XY: 88282
GnomAD4 exome AF: 0.0000114 AC: 16AN: 1405872Hom.: 0 Cov.: 31 AF XY: 0.0000144 AC XY: 10AN XY: 694294
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74386
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2019 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Knight Diagnostic Laboratories, Oregon Health and Sciences University | Sep 21, 2016 | - - |
Infantile neuroaxonal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | May 07, 2019 | - - |
Iron accumulation in brain Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
PLA2G6-associated neurodegeneration Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | Jan 24, 2023 | The p.Arg329His variant in PLA2G6 has been reported in 3 individuals. in the compound heterozygous state, with PLA2G6-associated neurodegeneration (PMID: 34256386, 27516098, 33098801) and has been identified in 0.006% (5/82514) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs587784363). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Arg329His variant is uncertain. ACMG/AMP Criteria applied: PM2_supporting (Richards 2015). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at