NM_145199.3:c.368delA
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_145199.3(LIPT1):c.368delA(p.Lys123SerfsTer8) variant causes a frameshift change. The variant allele was found at a frequency of 0.000064 in 1,609,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_145199.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LIPT1 | ENST00000651691.1 | c.368delA | p.Lys123SerfsTer8 | frameshift_variant | Exon 2 of 2 | NM_145199.3 | ENSP00000498546.1 | |||
ENSG00000273155 | ENST00000410042.1 | c.-28+5899delA | intron_variant | Intron 2 of 5 | 2 | ENSP00000387111.1 | ||||
ENSG00000241962 | ENST00000424491.5 | n.63+11806delA | intron_variant | Intron 4 of 13 | 2 | ENSP00000390891.1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151538Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.0000693 AC: 101AN: 1458270Hom.: 0 Cov.: 32 AF XY: 0.0000661 AC XY: 48AN XY: 725668
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151538Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2AN XY: 73972
ClinVar
Submissions by phenotype
Lipoyl transferase 1 deficiency Pathogenic:1
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not specified Uncertain:1
Variant summary: LIPT1 c.368delA (p.Lys123SerfsX8) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein, however the molecular mechanism of disease attributed to LIPT1 is currently unknown. While this variant is not expected to result in nonsense mediated decay, it is predicted to disrupt the last 251 amino acids of the protein, including part of the Biotinyl protein ligase and lipoyl protein ligase, catalytic domain (IPR004143). The variant allele was found at a frequency of 6.4e-05 in 1609808 control chromosomes (gnomAD v4.0.0). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.368delA in individuals affected with Lipoyl Transferase 1 Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have reported clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at