11-74493453-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001144869.3(LIPT2):ā€‹c.251G>Cā€‹(p.Gly84Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LIPT2
NM_001144869.3 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47
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]
LIPT2-AS1 (HGNC:56172): (LIPT2 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38356978).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LIPT2NM_001144869.3 linkc.251G>C p.Gly84Ala missense_variant Exon 1 of 2 ENST00000310109.5 NP_001138341.1 A6NK58
LIPT2NM_001329941.2 linkc.251G>C p.Gly84Ala missense_variant Exon 1 of 2 NP_001316870.1
LIPT2NM_001329942.2 linkc.237+14G>C intron_variant Intron 1 of 1 NP_001316871.1
LIPT2-AS1NR_171028.1 linkn.74C>G non_coding_transcript_exon_variant Exon 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LIPT2ENST00000310109.5 linkc.251G>C p.Gly84Ala missense_variant Exon 1 of 2 2 NM_001144869.3 ENSP00000309463.4 A6NK58
LIPT2-AS1ENST00000526036.1 linkn.88C>G non_coding_transcript_exon_variant Exon 1 of 2 1
LIPT2ENST00000528085.1 linkc.180+14G>C intron_variant Intron 1 of 1 3 ENSP00000433005.1 H0YD50

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1339750
Hom.:
0
Cov.:
43
AF XY:
0.00
AC XY:
0
AN XY:
660250
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Dec 25, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 1715038). This variant has not been reported in the literature in individuals affected with LIPT2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 84 of the LIPT2 protein (p.Gly84Ala). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Uncertain
24
DANN
Benign
0.96
DEOGEN2
Uncertain
0.51
D
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.40
N
LIST_S2
Benign
0.82
T
M_CAP
Pathogenic
0.66
D
MetaRNN
Benign
0.38
T
MetaSVM
Uncertain
0.18
D
MutationAssessor
Uncertain
2.1
M
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-2.0
N
REVEL
Uncertain
0.42
Sift
Benign
0.034
D
Sift4G
Uncertain
0.031
D
Polyphen
0.15
B
Vest4
0.21
MutPred
0.45
Loss of catalytic residue at G84 (P = 0.0191);
MVP
0.18
ClinPred
0.86
D
GERP RS
3.6
Varity_R
0.24
gMVP
0.53

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: rs990796543; hg19: chr11-74204498; API