Variant rs1218246470 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001144869.3(LIPT2):c.310G>T(p.Asp104Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,363,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000015 ( 0 hom. )

Consequence

LIPT2
NM_001144869.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.997

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:

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

LIPT2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPT2	NM_001144869.3 link	c.310G>T	p.Asp104Tyr	missense_variant	Exon 1 of 2	ENST00000310109.5	NP_001138341.1	A6NK58
LIPT2	NM_001329941.2 link	c.310G>T	p.Asp104Tyr	missense_variant	Exon 1 of 2		NP_001316870.1
LIPT2	NM_001329942.2 link	c.237+73G>T		intron_variant	Intron 1 of 1		NP_001316871.1
LIPT2-AS1	NR_171028.1 link	n.15C>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LIPT2	ENST00000310109.5 link	c.310G>T	p.Asp104Tyr	missense_variant	Exon 1 of 2	2	NM_001144869.3	ENSP00000309463.4	A6NK58
LIPT2-AS1	ENST00000526036.1 link	n.29C>A		non_coding_transcript_exon_variant	Exon 1 of 2	1
LIPT2	ENST00000528085.1 link	c.180+73G>T		intron_variant	Intron 1 of 1	3		ENSP00000433005.1	H0YD50
LIPT2	ENST00000527115.1 link	c.-81G>T		upstream_gene_variant		2		ENSP00000431210.1	H0YC96

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000908

AC:

AN:

110154

Hom.:

AF XY:

0.00

AC XY:

AN XY:

60968

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000126

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000147

AC:

AN:

1363488

Hom.:

Cov.:

AF XY:

0.00000297

AC XY:

AN XY:

672586

show subpopulations

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:

0.00000187

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.77

Eigen

Benign

0.094

Eigen_PC

Benign

0.036

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.86

MetaRNN

Pathogenic

0.79

MetaSVM

Pathogenic

0.93

MutationAssessor

Pathogenic

3.1

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-4.6

REVEL

Pathogenic

0.73

Sift

Benign

0.093

Sift4G

Benign

0.063

Polyphen

0.57

Vest4

0.48

MutPred

0.65

Gain of MoRF binding (P = 0.0523);

MVP

0.63

ClinPred

0.99

GERP RS

4.3

Varity_R

0.49

gMVP

0.80

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over