11-74492340-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001144869.3(LIPT2):​c.491C>T​(p.Thr164Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 1,399,386 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

LIPT2
NM_001144869.3 missense

Scores

12
5
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.54
Variant links:
Genes affected
LIPT2 (HGNC:37216): (lipoyl(octanoyl) transferase 2) This gene encodes a mitochondrial protein that catalyzes the transfer of octanoic acid to lipoate-dependent enzymes such as octanoyl-ACP. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.958

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LIPT2NM_001144869.3 linkc.491C>T p.Thr164Ile missense_variant Exon 2 of 2 ENST00000310109.5 NP_001138341.1 A6NK58
LIPT2NM_001329941.2 linkc.529C>T p.His177Tyr missense_variant Exon 2 of 2 NP_001316870.1
LIPT2NM_001329942.2 linkc.262C>T p.His88Tyr missense_variant Exon 2 of 2 NP_001316871.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LIPT2ENST00000310109.5 linkc.491C>T p.Thr164Ile missense_variant Exon 2 of 2 2 NM_001144869.3 ENSP00000309463.4 A6NK58
LIPT2ENST00000527115.1 linkc.139C>T p.His47Tyr missense_variant Exon 2 of 2 2 ENSP00000431210.1 H0YC96
LIPT2ENST00000528085.1 linkc.205C>T p.His69Tyr missense_variant Exon 2 of 2 3 ENSP00000433005.1 H0YD50

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000114
AC:
16
AN:
1399386
Hom.:
0
Cov.:
34
AF XY:
0.0000130
AC XY:
9
AN XY:
690206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000148
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 26, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.491C>T (p.T164I) alteration is located in exon 2 (coding exon 2) of the LIPT2 gene. This alteration results from a C to T substitution at nucleotide position 491, causing the threonine (T) at amino acid position 164 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.87
BayesDel_addAF
Pathogenic
0.56
D
BayesDel_noAF
Pathogenic
0.57
CADD
Pathogenic
31
DANN
Benign
0.94
DEOGEN2
Uncertain
0.80
D
Eigen
Pathogenic
0.90
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.93
D
M_CAP
Pathogenic
0.46
D
MetaRNN
Pathogenic
0.96
D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
3.7
H
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-5.9
D
REVEL
Pathogenic
0.94
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.77
MutPred
0.82
Loss of sheet (P = 0.0817);
MVP
0.37
ClinPred
0.99
D
GERP RS
5.3
Varity_R
0.75
gMVP
0.90

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: rs1864360066; hg19: chr11-74203385; API