11-74492141-G-A

Variant names:

• chr11-74492141-G-A
• rs147957229
• NM_001144869.3:c.690C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001144869.3(LIPT2):​c.690C>T​(p.Pro230Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,550,706 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (121 hom.)
• Consequence: LIPT2 NM_001144869.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.683

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-74492141-G-A is Benign according to our data. Variant chr11-74492141-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 771448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.683 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPT2	NM_001144869.3	c.690C>T	p.Pro230Pro	synonymous_variant	Exon 2 of 2	ENST00000310109.5	NP_001138341.1
LIPT2	NM_001329941.2	c.*104C>T		3_prime_UTR_variant	Exon 2 of 2		NP_001316870.1
LIPT2	NM_001329942.2	c.*104C>T		3_prime_UTR_variant	Exon 2 of 2		NP_001316871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPT2	ENST00000310109.5	c.690C>T	p.Pro230Pro	synonymous_variant	Exon 2 of 2	2	NM_001144869.3	ENSP00000309463.4
LIPT2	ENST00000527115	c.*104C>T		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000431210.1
LIPT2	ENST00000528085.1	c.*187C>T		downstream_gene_variant		3		ENSP00000433005.1

Frequencies

GnomAD3 genomes AF: 0.00464 AC: 706 AN: 152100 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.0117 AC: 1836 AN: 156400 Hom.: 86 AF XY: 0.00882 AC XY: 731 AN XY: 82884

Gnomad AFR exome AF: 0.00227

Gnomad AMR exome AF: 0.0710

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00147

Gnomad SAS exome AF: 0.000483

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000991

Gnomad OTH exome AF: 0.00706

GnomAD4 exome AF: 0.00199 AC: 2780 AN: 1398488 Hom.: 121 Cov.: 30 AF XY: 0.00164 AC XY: 1133 AN XY: 689806

Gnomad4 AFR exome AF: 0.000791

Gnomad4 AMR exome AF: 0.0681

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00372

Gnomad4 SAS exome AF: 0.000353

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000482

Gnomad4 OTH exome AF: 0.00188

GnomAD4 genome AF: 0.00468 AC: 712 AN: 152218 Hom.: 19 Cov.: 32 AF XY: 0.00566 AC XY: 421 AN XY: 74412

Gnomad4 AFR AF: 0.00181

Gnomad4 AMR AF: 0.0396

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00177 Hom.: 2

Bravo AF: 0.00747

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 05, 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

Dec 13, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

LIPT2-related disorder Benign:1

Sep 27, 2019

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
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs147957229; hg19: chr11-74203186;