11-74492359-G-C

Variant names:

• chr11-74492359-G-C
• rs1007474993
• NM_001144869.3:c.472C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001144869.3(LIPT2):​c.472C>G​(p.Arg158Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000644 in 1,398,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 31)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: LIPT2 NM_001144869.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.54

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 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=0.40484667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPT2	NM_001144869.3	c.472C>G	p.Arg158Gly	missense_variant	Exon 2 of 2	ENST00000310109.5	NP_001138341.1
LIPT2	NM_001329941.2	c.510C>G	p.Ser170Ser	synonymous_variant	Exon 2 of 2		NP_001316870.1
LIPT2	NM_001329942.2	c.243C>G	p.Ser81Ser	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	c.472C>G	p.Arg158Gly	missense_variant	Exon 2 of 2	2	NM_001144869.3	ENSP00000309463.4
LIPT2	ENST00000527115.1	c.120C>G	p.Ser40Ser	synonymous_variant	Exon 2 of 2	2		ENSP00000431210.1
LIPT2	ENST00000528085.1	c.186C>G	p.Ser62Ser	synonymous_variant	Exon 2 of 2	3		ENSP00000433005.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000638 AC: 1 AN: 156820 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 83010

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000165

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000644 AC: 9 AN: 1398438 Hom.: 0 Cov.: 33 AF XY: 0.00000580 AC XY: 4 AN XY: 689802

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: 0.0000406

Gnomad4 NFE exome AF: 0.00000464

Gnomad4 OTH exome AF: 0.0000345

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.8	D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.021	D
Polyphen		0.10	B
Vest4		0.44
MutPred		0.69		Loss of MoRF binding (P = 0.0514);
MVP		0.39
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.29
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1007474993; hg19: chr11-74203404;