5-132370222-T-TACCGGCTCGCC
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_003060.4(SLC22A5):c.254_264dupGGCTCGCCACC(p.Ile89GlyfsTer45) variant causes a frameshift change. The variant allele was found at a frequency of 0.000046 in 152,192 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_003060.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152192Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000375 AC: 7AN: 186880Hom.: 0 AF XY: 0.0000292 AC XY: 3AN XY: 102696
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000203 AC: 29AN: 1427734Hom.: 0 Cov.: 31 AF XY: 0.0000198 AC XY: 14AN XY: 707348
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74354
ClinVar
Submissions by phenotype
Renal carnitine transport defect Pathogenic:7
This sequence change creates a premature translational stop signal (p.Ile89Glyfs*45) in the SLC22A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC22A5 are known to be pathogenic (PMID: 9916797). This variant is present in population databases (rs757431170, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with primary carnitine deficiency (PMID: 11715001, 28841266). ClinVar contains an entry for this variant (Variation ID: 38790). For these reasons, this variant has been classified as Pathogenic. -
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Variant summary: The SLC22A5 c.254_264dup11 (p.Ile89Glyfs) variant results in a premature termination codon, predicted to cause a truncated or absent SLC22A5 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 42704 control chromosomes. This variant has been reported in multiple PCD patients both homozygously and heterozygously. Functional study showed this variant caused decreased levels of mature mRNA. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. -
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not provided Pathogenic:2
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Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 16652335, 31980526, 11715001, 21922592, 23379544, 28841266, 15714519) -
Decreased circulating carnitine concentration Pathogenic:1
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Congenital myasthenic syndrome 20 Pathogenic:1
Congenital Myasthenic Syndrome with episodic apneas. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at