rs201177082
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_020376.4(PNPLA2):c.1406C>T(p.Pro469Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000978 in 1,564,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNPLA2 | NM_020376.4 | c.1406C>T | p.Pro469Leu | missense_variant | 10/10 | ENST00000336615.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPLA2 | ENST00000336615.9 | c.1406C>T | p.Pro469Leu | missense_variant | 10/10 | 1 | NM_020376.4 | P1 | |
PNPLA2 | ENST00000529255.1 | n.836C>T | non_coding_transcript_exon_variant | 4/4 | 1 | ||||
ENST00000532946.1 | n.307-890G>A | intron_variant, non_coding_transcript_variant | 5 | ||||||
PNPLA2 | ENST00000525250.5 | n.2260C>T | non_coding_transcript_exon_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000591 AC: 90AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000101 AC: 17AN: 167948Hom.: 0 AF XY: 0.000107 AC XY: 10AN XY: 93454
GnomAD4 exome AF: 0.0000446 AC: 63AN: 1412326Hom.: 0 Cov.: 42 AF XY: 0.0000471 AC XY: 33AN XY: 699992
GnomAD4 genome ? AF: 0.000591 AC: 90AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.000537 AC XY: 40AN XY: 74470
ClinVar
Submissions by phenotype
Neutral lipid storage myopathy Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 469 of the PNPLA2 protein (p.Pro469Leu). This variant is present in population databases (rs201177082, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with PNPLA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 534196). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 04, 2020 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 24, 2023 | The c.1406C>T (p.P469L) alteration is located in exon 10 (coding exon 9) of the PNPLA2 gene. This alteration results from a C to T substitution at nucleotide position 1406, causing the proline (P) at amino acid position 469 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at