chr11-821696-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_020376.4(PNPLA2):c.256C>T(p.Pro86Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,826 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 (★). Synonymous variant affecting the same amino acid position (i.e. P86P) has been classified as Likely benign.
Frequency
Consequence
NM_020376.4 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 |
---|---|---|---|---|---|---|---|
PNPLA2 | NM_020376.4 | c.256C>T | p.Pro86Ser | missense_variant | 3/10 | ENST00000336615.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPLA2 | ENST00000336615.9 | c.256C>T | p.Pro86Ser | missense_variant | 3/10 | 1 | NM_020376.4 | P1 | |
PNPLA2 | ENST00000525250.5 | n.862C>T | non_coding_transcript_exon_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152062Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251070Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135792
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461646Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727120
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74394
ClinVar
Submissions by phenotype
Neutral lipid storage myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 06, 2017 | This sequence change replaces proline with serine at codon 86 of the PNPLA2 protein (p.Pro86Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PNPLA2-related disease. This variant is present in population databases (rs530863669, ExAC 0.003%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at