NM_001144869.3:c.282G>A

Variant names:

• chr11-74493422-C-T
• rs1329263134
• NM_001144869.3:c.282G>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001144869.3(LIPT2):​c.282G>A​(p.Pro94Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000368 in 1,357,144 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: 34)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: LIPT2 NM_001144869.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.05

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

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-4.05 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPT2	NM_001144869.3	c.282G>A	p.Pro94Pro	synonymous_variant	Exon 1 of 2	ENST00000310109.5	NP_001138341.1
LIPT2	NM_001329941.2	c.282G>A	p.Pro94Pro	synonymous_variant	Exon 1 of 2		NP_001316870.1
LIPT2	NM_001329942.2	c.237+45G>A		intron_variant	Intron 1 of 1		NP_001316871.1
LIPT2-AS1	NR_171028.1	n.43C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPT2	ENST00000310109.5	c.282G>A	p.Pro94Pro	synonymous_variant	Exon 1 of 2	2	NM_001144869.3	ENSP00000309463.4
LIPT2-AS1	ENST00000526036.1	n.57C>T		non_coding_transcript_exon_variant	Exon 1 of 2	1
LIPT2	ENST00000528085.1	c.180+45G>A		intron_variant	Intron 1 of 1	3		ENSP00000433005.1
LIPT2	ENST00000527115.1	c.-109G>A		upstream_gene_variant		2		ENSP00000431210.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000368 AC: 5 AN: 1357144 Hom.: 0 Cov.: 43 AF XY: 0.00000448 AC XY: 3 AN XY: 669252

Gnomad4 AFR exome AF: 0.0000357

Gnomad4 AMR exome AF: 0.0000302

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000131

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.1
DANN	Benign	0.92

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: rs1329263134; hg19: chr11-74204467;