3-48857754-C-A
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_000387.6(SLC25A20):c.862G>T(p.Glu288*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SLC25A20
NM_000387.6 stop_gained
NM_000387.6 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 7.88
Genes affected
SLC25A20 (HGNC:1421): (solute carrier family 25 member 20) This gene product is one of several closely related mitochondrial-membrane carrier proteins that shuttle substrates between cytosol and the intramitochondrial matrix space. This protein mediates the transport of acylcarnitines into mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway. Mutations in this gene are associated with carnitine-acylcarnitine translocase deficiency, which can cause a variety of pathological conditions such as hypoglycemia, cardiac arrest, hepatomegaly, hepatic dysfunction and muscle weakness, and is usually lethal in new born and infants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0486 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-48857754-C-A is Pathogenic according to our data. Variant chr3-48857754-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3589295.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152016Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249982Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135266
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461658Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727112
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152016Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74242
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Carnitine acylcarnitine translocase deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jun 01, 2024 | - - |
Computational scores
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Name
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
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Pathogenic
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Uncertain
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Pathogenic
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Pathogenic
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Pathogenic
D
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at