Variant 11-74493420-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001144869.3(LIPT2):c.284G>A(p.Gly95Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000147 in 1,357,536 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: 34)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

LIPT2
NM_001144869.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.62

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 links:

LIPT2-AS1 (HGNC:56172): (LIPT2 antisense RNA 1)

LIPT2-AS1 links:

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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, 0.991

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPT2	NM_001144869.3 link	c.284G>A	p.Gly95Asp	missense_variant	Exon 1 of 2	ENST00000310109.5	NP_001138341.1	A6NK58
LIPT2	NM_001329941.2 link	c.284G>A	p.Gly95Asp	missense_variant	Exon 1 of 2		NP_001316870.1
LIPT2	NM_001329942.2 link	c.237+47G>A		intron_variant	Intron 1 of 1		NP_001316871.1
LIPT2-AS1	NR_171028.1 link	n.41C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LIPT2	ENST00000310109.5 link	c.284G>A	p.Gly95Asp	missense_variant	Exon 1 of 2	2	NM_001144869.3	ENSP00000309463.4	A6NK58
LIPT2-AS1	ENST00000526036.1 link	n.55C>T		non_coding_transcript_exon_variant	Exon 1 of 2	1
LIPT2	ENST00000528085.1 link	c.180+47G>A		intron_variant	Intron 1 of 1	3		ENSP00000433005.1	H0YD50

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000147

AC:

AN:

1357536

Hom.:

Cov.:

AF XY:

0.00000299

AC XY:

AN XY:

669458

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:

0.00000187

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities

Uncertain:2

Feb 07, 2020

Baylor Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Sep 22, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Pathogenic

0.65

BayesDel_noAF

Pathogenic

0.69

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.82

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.89

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

4.1

PrimateAI

Pathogenic

0.95

PROVEAN

Pathogenic

-6.8

REVEL

Pathogenic

0.89

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.88

MutPred

0.95

Gain of relative solvent accessibility (P = 0.1259);

MVP

0.33

ClinPred

1.0

GERP RS

4.6

Varity_R

0.96

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over