22-46198426-G-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005036.6(PPARA):āc.43G>Cā(p.Glu15Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,822 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 (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
PPARA
NM_005036.6 missense
NM_005036.6 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 6.14
Genes affected
PPARA (HGNC:9232): (peroxisome proliferator activated receptor alpha) Peroxisome proliferators include hypolipidemic drugs, herbicides, leukotriene antagonists, and plasticizers; this term arises because they induce an increase in the size and number of peroxisomes. Peroxisomes are subcellular organelles found in plants and animals that contain enzymes for respiration and for cholesterol and lipid metabolism. The action of peroxisome proliferators is thought to be mediated via specific receptors, called PPARs, which belong to the steroid hormone receptor superfamily. PPARs affect the expression of target genes involved in cell proliferation, cell differentiation and in immune and inflammation responses. Three closely related subtypes (alpha, beta/delta, and gamma) have been identified. This gene encodes the subtype PPAR-alpha, which is a nuclear transcription factor. Multiple alternatively spliced transcript variants have been described for this gene, although the full-length nature of only two has been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PPARA | NM_005036.6 | c.43G>C | p.Glu15Gln | missense_variant | 4/9 | ENST00000407236.6 | NP_005027.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PPARA | ENST00000407236.6 | c.43G>C | p.Glu15Gln | missense_variant | 4/9 | 1 | NM_005036.6 | ENSP00000385523.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251394Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135858
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461822Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727212
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GnomAD4 genome Cov.: 31
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31
ExAC
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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 | Aug 30, 2022 | The c.43G>C (p.E15Q) alteration is located in exon 4 (coding exon 1) of the PPARA gene. This alteration results from a G to C substitution at nucleotide position 43, causing the glutamic acid (E) at amino acid position 15 to be replaced by a glutamine (Q). 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
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;T;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;.;.
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;L;.;L;L
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.088
.;B;.;B;B
Vest4
0.39, 0.39, 0.41
MutPred
Gain of catalytic residue at E15 (P = 0.0797);Gain of catalytic residue at E15 (P = 0.0797);Gain of catalytic residue at E15 (P = 0.0797);Gain of catalytic residue at E15 (P = 0.0797);Gain of catalytic residue at E15 (P = 0.0797);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at