22-46235199-GA-CG

Variant names:

• chr22-46235199-GA-CG
• NM_005036.6:c.1226_1227delGAinsCG
• PPARA p.Arg409Thr

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005036.6(PPARA):​c.1226_1227delGAinsCG​(p.Arg409Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPARA NM_005036.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.699
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005036.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARA	NM_005036.6	MANE Select	c.1226_1227delGAinsCG	p.Arg409Thr	missense	N/A	NP_005027.2
	PPARA	NM_001001928.4		c.1226_1227delGAinsCG	p.Arg409Thr	missense	N/A	NP_001001928.1	Q07869-1
	PPARA	NM_001001929.3		c.1226_1227delGAinsCG	p.Arg409Thr	missense	N/A	NP_001001929.1	Q07869-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARA	ENST00000407236.6	TSL:1 MANE Select	c.1226_1227delGAinsCG	p.Arg409Thr	missense	N/A	ENSP00000385523.1	Q07869-1
	PPARA	ENST00000402126.2	TSL:1	c.1226_1227delGAinsCG	p.Arg409Thr	missense	N/A	ENSP00000385246.1	Q07869-1
	PPARA	ENST00000873468.1		c.1226_1227delGAinsCG	p.Arg409Thr	missense	N/A	ENSP00000543527.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-46631096;