22-43926968-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_025225.3(PNPLA3):c.221G>A(p.Arg74Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_025225.3 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 |
---|---|---|---|---|---|---|---|
PNPLA3 | NM_025225.3 | c.221G>A | p.Arg74Gln | missense_variant | 2/9 | ENST00000216180.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPLA3 | ENST00000216180.8 | c.221G>A | p.Arg74Gln | missense_variant | 2/9 | 1 | NM_025225.3 | P1 | |
PNPLA3 | ENST00000423180.2 | c.209G>A | p.Arg70Gln | missense_variant | 2/9 | 2 | |||
PNPLA3 | ENST00000478713.1 | n.255G>A | non_coding_transcript_exon_variant | 2/4 | 2 | ||||
PNPLA3 | ENST00000406117.6 | c.216G>A | p.Ala72= | synonymous_variant, NMD_transcript_variant | 2/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152196Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251390Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135894
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461854Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727226
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74352
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2022 | The c.221G>A (p.R74Q) alteration is located in exon 2 (coding exon 2) of the PNPLA3 gene. This alteration results from a G to A substitution at nucleotide position 221, causing the arginine (R) at amino acid position 74 to be replaced by a glutamine (Q). 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