2-99162169-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PM2PP5_Very_StrongBP4
The NM_145199.3(LIPT1):c.212C>T(p.Ser71Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,860 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 pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S71C) has been classified as Uncertain significance.
Frequency
Consequence
NM_145199.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIPT1 | NM_145199.3 | c.212C>T | p.Ser71Phe | missense_variant | 2/2 | ENST00000651691.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIPT1 | ENST00000651691.1 | c.212C>T | p.Ser71Phe | missense_variant | 2/2 | NM_145199.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152122Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000876 AC: 22AN: 251232Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135796
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461738Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727170
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152122Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74316
ClinVar
Submissions by phenotype
Lipoyl transferase 1 deficiency Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Elsea Laboratory, Baylor College of Medicine | Apr 01, 2020 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2014 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 29, 2019 | Reported as compound heterozygous with another variant in LIPT1 on the opposite allele in individuals with lipoyltransferase 1 deficiency (Tort et al., 2014;Meng et al., 2017); Published functional studies demonstrate a damaging effect (functional assays on an in vitro expressing system demonstrated that the S71F variant causes an absence of protein-bound lipoic acid staining compared to WT; assays on patient's fibroblasts supported the defect of this variant on enzymatic activity) (Tort F. et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29681092, 28973083, 24256811) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at