11-824780-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020376.4(PNPLA2):c.1433A>G(p.Gln478Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 1,386,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_020376.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNPLA2 | NM_020376.4 | c.1433A>G | p.Gln478Arg | missense_variant | 10/10 | ENST00000336615.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPLA2 | ENST00000336615.9 | c.1433A>G | p.Gln478Arg | missense_variant | 10/10 | 1 | NM_020376.4 | P1 | |
PNPLA2 | ENST00000529255.1 | n.863A>G | non_coding_transcript_exon_variant | 4/4 | 1 | ||||
ENST00000532946.1 | n.307-917T>C | intron_variant, non_coding_transcript_variant | 5 | ||||||
PNPLA2 | ENST00000525250.5 | n.2287A>G | non_coding_transcript_exon_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.0000115 AC: 16AN: 1386332Hom.: 0 Cov.: 42 AF XY: 0.0000102 AC XY: 7AN XY: 684700
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Neutral lipid storage myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 09, 2018 | This sequence change replaces glutamine with arginine at codon 478 of the PNPLA2 protein (p.Gln478Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with PNPLA2-related disease. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at