22-43924017-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_025225.3(PNPLA3):c.106C>A(p.Leu36Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,583,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000091 ( 0 hom. )
Consequence
PNPLA3
NM_025225.3 missense
NM_025225.3 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 0.649
Genes affected
PNPLA3 (HGNC:18590): (patatin like phospholipase domain containing 3) The protein encoded by this gene is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes. The encoded protein, which appears to be membrane bound, may be involved in the balance of energy usage/storage in adipocytes. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2731737).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNPLA3 | NM_025225.3 | c.106C>A | p.Leu36Ile | missense_variant | 1/9 | ENST00000216180.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPLA3 | ENST00000216180.8 | c.106C>A | p.Leu36Ile | missense_variant | 1/9 | 1 | NM_025225.3 | P1 | |
PNPLA3 | ENST00000423180.2 | c.106C>A | p.Leu36Ile | missense_variant | 1/9 | 2 | |||
PNPLA3 | ENST00000406117.6 | c.106C>A | p.Leu36Ile | missense_variant, NMD_transcript_variant | 1/10 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152250Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000524 AC: 11AN: 210066Hom.: 0 AF XY: 0.0000256 AC XY: 3AN XY: 117352
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GnomAD4 exome AF: 0.00000908 AC: 13AN: 1431446Hom.: 0 Cov.: 31 AF XY: 0.00000562 AC XY: 4AN XY: 712356
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152368Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74514
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 02, 2024 | The c.106C>A (p.L36I) alteration is located in exon 1 (coding exon 1) of the PNPLA3 gene. This alteration results from a C to A substitution at nucleotide position 106, causing the leucine (L) at amino acid position 36 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
D;D
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at