4-23814220-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_013261.5(PPARGC1A):c.1263G>A(p.Gly421=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,948 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 2 hom. )
Consequence
PPARGC1A
NM_013261.5 synonymous
NM_013261.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.42
Genes affected
PPARGC1A (HGNC:9237): (PPARG coactivator 1 alpha) The protein encoded by this gene is a transcriptional coactivator that regulates the genes involved in energy metabolism. This protein interacts with PPARgamma, which permits the interaction of this protein with multiple transcription factors. This protein can interact with, and regulate the activities of, cAMP response element binding protein (CREB) and nuclear respiratory factors (NRFs). It provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 4-23814220-C-T is Benign according to our data. Variant chr4-23814220-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 745082.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=2.42 with no splicing effect.
BS2
?
High AC in GnomAdExome at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPARGC1A | NM_013261.5 | c.1263G>A | p.Gly421= | synonymous_variant | 8/13 | ENST00000264867.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPARGC1A | ENST00000264867.7 | c.1263G>A | p.Gly421= | synonymous_variant | 8/13 | 1 | NM_013261.5 | P1 | |
PPARGC1A | ENST00000613098.4 | c.882G>A | p.Gly294= | synonymous_variant | 7/12 | 1 | |||
PPARGC1A | ENST00000506055.5 | c.*478G>A | 3_prime_UTR_variant, NMD_transcript_variant | 8/13 | 1 | ||||
PPARGC1A | ENST00000509702.5 | n.1303G>A | non_coding_transcript_exon_variant | 8/15 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 250980Hom.: 0 AF XY: 0.0000811 AC XY: 11AN XY: 135638
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GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461838Hom.: 2 Cov.: 69 AF XY: 0.0000468 AC XY: 34AN XY: 727218
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74292
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 30, 2018 | - - |
Computational scores
Source:
Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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