rs151340616
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000387.6(SLC25A20):c.496C>T(p.Arg166Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,786 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000387.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC25A20 | NM_000387.6 | c.496C>T | p.Arg166Ter | stop_gained | 5/9 | ENST00000319017.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC25A20 | ENST00000319017.5 | c.496C>T | p.Arg166Ter | stop_gained | 5/9 | 1 | NM_000387.6 | P1 | |
SLC25A20 | ENST00000430379.5 | c.277C>T | p.Arg93Ter | stop_gained | 3/7 | 3 | |||
SLC25A20 | ENST00000440964.1 | c.*326C>T | 3_prime_UTR_variant, NMD_transcript_variant | 6/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251456Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135912
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461682Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727162
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74292
ClinVar
Submissions by phenotype
Carnitine acylcarnitine translocase deficiency Pathogenic:5
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 30, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 16, 2023 | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Arg166*) in the SLC25A20 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC25A20 are known to be pathogenic (PMID: 25614308). This variant is present in population databases (rs151340616, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with carnitine-acylcarnitine translocase deficiency (PMID: 10384384, 12559850). ClinVar contains an entry for this variant (Variation ID: 12135). - |
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 05, 2021 | Variant summary: SLC25A20 c.496C>T (p.Arg166X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 251456 control chromosomes (gnomAD). c.496C>T has been reported in the literature in at least two individuals (homozygous and a compound heterozygous) affected with Carnitine-Acylcarnitine Translocase Deficiency (Costa_1999 and Wang_2011). One homozygous individual with this variant was reported as having a complete deficiency of Carnitine Acylcarnitine carrier enzyme activity at day 3 and confirmed three months later in fibroblasts, however, primary data supporting this finding were not reported (Costa_1999). To our knowledge, no other experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 10, 2021 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 1999 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 09, 2018 | The R166X nonsense variant in the SLC25A20 gene has been reported previously in association with carnitine-acylcarnitine translocase deficiency (Costa et al., 1999; Wang et al., 2011). The R166X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at