4-23814138-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_013261.5(PPARGC1A):c.1345A>G(p.Thr449Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_013261.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPARGC1A | NM_013261.5 | c.1345A>G | p.Thr449Ala | missense_variant | 8/13 | ENST00000264867.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPARGC1A | ENST00000264867.7 | c.1345A>G | p.Thr449Ala | missense_variant | 8/13 | 1 | NM_013261.5 | P1 | |
PPARGC1A | ENST00000613098.4 | c.964A>G | p.Thr322Ala | missense_variant | 7/12 | 1 | |||
PPARGC1A | ENST00000506055.5 | c.*560A>G | 3_prime_UTR_variant, NMD_transcript_variant | 8/13 | 1 | ||||
PPARGC1A | ENST00000509702.5 | n.1385A>G | non_coding_transcript_exon_variant | 8/15 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250754Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135494
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461834Hom.: 0 Cov.: 69 AF XY: 0.0000303 AC XY: 22AN XY: 727210
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74338
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2024 | The c.1345A>G (p.T449A) alteration is located in exon 8 (coding exon 8) of the PPARGC1A gene. This alteration results from a A to G substitution at nucleotide position 1345, causing the threonine (T) at amino acid position 449 to be replaced by an alanine (A). 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