11-74492224-C-G

Variant names:

• chr11-74492224-C-G
• rs1420082518
• NM_001144869.3:c.607G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001144869.3(LIPT2):​c.607G>C​(p.Val203Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: LIPT2 NM_001144869.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05703327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPT2	NM_001144869.3	c.607G>C	p.Val203Leu	missense_variant	Exon 2 of 2	ENST00000310109.5	NP_001138341.1
LIPT2	NM_001329941.2	c.*21G>C		3_prime_UTR_variant	Exon 2 of 2		NP_001316870.1
LIPT2	NM_001329942.2	c.*21G>C		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.607G>C	p.Val203Leu	missense_variant	Exon 2 of 2	2	NM_001144869.3	ENSP00000309463.4
LIPT2	ENST00000527115	c.*21G>C		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000431210.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399428 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690218

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	2.3
DANN	Benign	0.83
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.057	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.24
Sift	Benign	0.16	T
Sift4G	Benign	0.16	T
Polyphen		0.0010	B
Vest4		0.093
MutPred		0.30		Gain of disorder (P = 0.2197);
MVP		0.061
ClinPred		0.12	T
GERP RS		1.4
Varity_R		0.083
gMVP		0.89

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: rs1420082518; hg19: chr11-74203269;