rs779797773

Variant names:

• chr22-46198426-G-A
• rs779797773
• NM_005036.6:c.43G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-46198426-G-A
• chr22-46198426-G-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_005036.6(PPARA):​c.43G>A​(p.Glu15Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E15Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PPARA NM_005036.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.14
• Publications: 2 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3590434).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPARA	NM_005036.6	c.43G>A	p.Glu15Lys	missense_variant	Exon 4 of 9	ENST00000407236.6	NP_005027.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPARA	ENST00000407236.6	c.43G>A	p.Glu15Lys	missense_variant	Exon 4 of 9	1	NM_005036.6	ENSP00000385523.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461822 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1111962

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;T;.;T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T;T;T;.;.
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.36	T;T;T;T;T
MetaSVM	Uncertain	0.58	D
MutationAssessor	Benign	1.2	.;L;.;L;L
PhyloP100		6.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.4	D;N;N;N;N
REVEL	Benign	0.29
Sift	Benign	0.095	T;T;T;T;T
Sift4G	Benign	0.065	T;T;T;T;T
Polyphen		0.0010	.;B;.;B;B
Vest4		0.27, 0.31
MutPred		0.25		Gain of ubiquitination at E15 (P = 0.0048);Gain of ubiquitination at E15 (P = 0.0048);Gain of ubiquitination at E15 (P = 0.0048);Gain of ubiquitination at E15 (P = 0.0048);Gain of ubiquitination at E15 (P = 0.0048);
MVP		0.89
ClinPred		0.76	D
GERP RS		4.7
Varity_R		0.051
gMVP		0.41
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs779797773; hg19: chr22-46594323;