rs863224892

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_145199.3(LIPT1):​c.806G>A​(p.Trp269*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

LIPT1
NM_145199.3 stop_gained

Scores

5
1
1

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 9.53
Variant links:
Genes affected
LIPT1 (HGNC:29569): (lipoyltransferase 1) The process of transferring lipoic acid to proteins is a two-step process. The first step is the activation of lipoic acid by lipoate-activating enzyme to form lipoyl-AMP. For the second step, the protein encoded by this gene transfers the lipoyl moiety to apoproteins. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 13. Read-through transcription also exists between this gene and the neighboring downstream mitochondrial ribosomal protein L30 (MRPL30) gene. [provided by RefSeq, Mar 2011]
MITD1 (HGNC:25207): (microtubule interacting and trafficking domain containing 1) Abscission, the separation of daughter cells at the end of cytokinesis, is effected by endosomal sorting complexes required for transport III (ESCRT-III). The protein encoded by this gene functions as a homodimer, with the N-termini binding to a subset of ESCRT-III subunits and the C-termini binding to membranes. The encoded protein regulates ESCRT-III activity and is required for proper cytokinesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 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 0.282 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 2-99162763-G-A is Pathogenic according to our data. Variant chr2-99162763-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 242526.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LIPT1NM_145199.3 linkc.806G>A p.Trp269* stop_gained Exon 2 of 2 ENST00000651691.1 NP_660200.1 Q9Y234

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LIPT1ENST00000651691.1 linkc.806G>A p.Trp269* stop_gained Exon 2 of 2 NM_145199.3 ENSP00000498546.1 Q9Y234
ENSG00000273155ENST00000410042.1 linkc.-28+6337G>A intron_variant Intron 2 of 5 2 ENSP00000387111.1
ENSG00000241962ENST00000424491.5 linkn.63+12244G>A intron_variant Intron 4 of 13 2 ENSP00000390891.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Lipoyl transferase 1 deficiency Pathogenic:1
-
Neuberg Centre For Genomic Medicine, NCGM
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The stop gained variant c.806G>A (p.Trp269Ter) in LIPT1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has not been reported to the ClinVar database.The variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The nucleotide change in LIPT1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.65
CADD
Pathogenic
39
DANN
Uncertain
0.99
Eigen
Pathogenic
0.96
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.99
D
Vest4
0.42
GERP RS
4.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs863224892; hg19: chr2-99779226; API