Variant 11-74493431-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001144869.3(LIPT2):c.273C>T(p.Phe91=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,505,956 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00014 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

LIPT2
NM_001144869.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.12

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 Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 11-74493431-G-A is Benign according to our data. Variant chr11-74493431-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1601557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.12 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LIPT2	NM_001144869.3 linkuse as main transcript	c.273C>T	p.Phe91=	synonymous_variant	1/2	ENST00000310109.5
LIPT2-AS1	NR_171028.1 linkuse as main transcript	n.52G>A		non_coding_transcript_exon_variant	1/2
LIPT2	NM_001329941.2 linkuse as main transcript	c.273C>T	p.Phe91=	synonymous_variant	1/2
LIPT2	NM_001329942.2 linkuse as main transcript	c.237+36C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LIPT2	ENST00000310109.5 linkuse as main transcript	c.273C>T	p.Phe91=	synonymous_variant	1/2	2	NM_001144869.3	P1
LIPT2-AS1	ENST00000526036.1 linkuse as main transcript	n.66G>A		non_coding_transcript_exon_variant	1/2	1
LIPT2	ENST00000528085.1 linkuse as main transcript	c.181+36C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00142

AC:

143

AN:

100900

Hom.:

AF XY:

0.000977

AC XY:

AN XY:

56306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00689

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000158

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000130

AC:

176

AN:

1353630

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

667412

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00519

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000312

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.38e-7

Gnomad4 OTH exome

AF:

0.0000884

GnomAD4 genome

AF:

0.000144

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000438

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 13, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.86

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over