11-74492263-T-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001144869.3(LIPT2):c.568A>T(p.Thr190Ser) variant causes a missense change. The variant allele was found at a frequency of 0.608 in 1,551,212 control chromosomes in the GnomAD database, including 289,463 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23913 hom., cov: 31)

Exomes 𝑓: 0.61 ( 265550 hom. )

Consequence

LIPT2
NM_001144869.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.78

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.3479864E-5).

BP6

Variant 11-74492263-T-A is Benign according to our data. Variant chr11-74492263-T-A is described in ClinVar as [Benign]. Clinvar id is 1169390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPT2	NM_001144869.3 link	c.568A>T	p.Thr190Ser	missense_variant	Exon 2 of 2	ENST00000310109.5	NP_001138341.1	A6NK58
LIPT2	NM_001329941.2 link	c.606A>T	p.Gly202Gly	synonymous_variant	Exon 2 of 2		NP_001316870.1
LIPT2	NM_001329942.2 link	c.339A>T	p.Gly113Gly	synonymous_variant	Exon 2 of 2		NP_001316871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPT2	ENST00000310109.5 link	c.568A>T	p.Thr190Ser	missense_variant	Exon 2 of 2	2	NM_001144869.3	ENSP00000309463.4		A6NK58
LIPT2	ENST00000527115.1 link	c.216A>T	p.Gly72Gly	synonymous_variant	Exon 2 of 2	2		ENSP00000431210.1		H0YC96

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

83885

AN:

151820

Hom.:

23924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.635

Gnomad EAS

AF:

0.649

Gnomad SAS

AF:

0.516

Gnomad FIN

AF:

0.600

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.635

Gnomad OTH

AF:

0.552

GnomAD3 exomes

AF:

0.580

AC:

90980

AN:

156780

Hom.:

26820

AF XY:

0.581

AC XY:

48249

AN XY:

83056

show subpopulations

Gnomad AFR exome

AF:

0.400

Gnomad AMR exome

AF:

0.510

Gnomad ASJ exome

AF:

0.634

Gnomad EAS exome

AF:

0.661

Gnomad SAS exome

AF:

0.508

Gnomad FIN exome

AF:

0.599

Gnomad NFE exome

AF:

0.631

Gnomad OTH exome

AF:

0.591

GnomAD4 exome

AF:

0.614

AC:

858739

AN:

1399276

Hom.:

265550

Cov.:

AF XY:

0.612

AC XY:

422601

AN XY:

690142

show subpopulations

Gnomad4 AFR exome

AF:

0.397

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.633

Gnomad4 EAS exome

AF:

0.675

Gnomad4 SAS exome

AF:

0.517

Gnomad4 FIN exome

AF:

0.592

Gnomad4 NFE exome

AF:

0.630

Gnomad4 OTH exome

AF:

0.599

GnomAD4 genome

AF:

0.552

AC:

83900

AN:

151936

Hom.:

23913

Cov.:

AF XY:

0.547

AC XY:

40604

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.404

Gnomad4 AMR

AF:

0.522

Gnomad4 ASJ

AF:

0.635

Gnomad4 EAS

AF:

0.649

Gnomad4 SAS

AF:

0.517

Gnomad4 FIN

AF:

0.600

Gnomad4 NFE

AF:

0.635

Gnomad4 OTH

AF:

0.549

Alfa

AF:

0.621

Hom.:

22278

Bravo

AF:

0.543

TwinsUK

AF:

0.635

AC:

2354

ALSPAC

AF:

0.639

AC:

2463

ExAC

AF:

0.543

AC:

13690

Asia WGS

AF:

0.526

AC:

1829

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

LIPT2-related disorder

Benign:1

Feb 10, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.060

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.000033

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.48

PROVEAN

Benign

0.43

REVEL

Benign

0.27

Sift

Benign

0.080

Sift4G

Uncertain

0.022

Polyphen

0.077

Vest4

0.046

ClinPred

0.018

GERP RS

4.0

Varity_R

0.074

gMVP

0.51

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.

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