12-56285943-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_004077.3(CS):c.174G>A(p.Thr58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,542 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
CS
NM_004077.3 synonymous
NM_004077.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.17
Genes affected
CS (HGNC:2422): (citrate synthase) The protein encoded by this gene is a Krebs tricarboxylic acid cycle enzyme that catalyzes the synthesis of citrate from oxaloacetate and acetyl coenzyme A. The enzyme is found in nearly all cells capable of oxidative metablism. This protein is nuclear encoded and transported into the mitochondrial matrix, where the mature form is found. [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=-0.35).
BP6
Variant 12-56285943-C-T is Benign according to our data. Variant chr12-56285943-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 737271.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.17 with no splicing effect.
BS2
High AC in GnomAdExome4 at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CS | NM_004077.3 | c.174G>A | p.Thr58= | synonymous_variant | 3/11 | ENST00000351328.8 | NP_004068.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CS | ENST00000351328.8 | c.174G>A | p.Thr58= | synonymous_variant | 3/11 | 1 | NM_004077.3 | ENSP00000342056 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152190Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251332Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135846
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460352Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 726478
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152190Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74350
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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 | Labcorp Genetics (formerly Invitae), Labcorp | Mar 29, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
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RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at