Variant chr18-49567444-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006033.4(LIPG):c.282G>T(p.Met94Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000496 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

LIPG
NM_006033.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.63

Variant links:

Genes affected

LIPG (HGNC:6623): (lipase G, endothelial type) The protein encoded by this gene has substantial phospholipase activity and may be involved in lipoprotein metabolism and vascular biology. This protein is designated a member of the TG lipase family by its sequence and characteristic lid region which provides substrate specificity for enzymes of the TG lipase family. [provided by RefSeq, Jul 2008]

LIPG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPG	NM_006033.4 linkuse as main transcript	c.282G>T	p.Met94Ile	missense_variant, splice_region_variant	3/10	ENST00000261292.9	NP_006024.1	Q9Y5X9-1A0A024R2B5
LIPG	NM_001308006.2 linkuse as main transcript	c.282G>T	p.Met94Ile	missense_variant, splice_region_variant	3/9		NP_001294935.1	Q9Y5X9B4DTR8
LIPG	XM_047437944.1 linkuse as main transcript	c.390G>T	p.Met130Ile	missense_variant, splice_region_variant	3/5		XP_047293900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPG	ENST00000261292.9 linkuse as main transcript	c.282G>T	p.Met94Ile	missense_variant, splice_region_variant	3/10	1	NM_006033.4	ENSP00000261292.4		Q9Y5X9-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727148

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 18, 2022

This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 94 of the LIPG protein (p.Met94Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LIPG-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;.;T;T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

D;T;D;D;D

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.48

T;T;T;T;T

MetaSVM

Uncertain

0.38

MutationAssessor

Benign

1.9

.;.;L;.;L

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.27

.;.;N;N;.

REVEL

Uncertain

0.53

Sift

Benign

0.036

.;.;D;D;.

Sift4G

Benign

0.40

T;D;T;T;T

Polyphen

0.71, 0.65, 0.16

.;.;P;P;B

Vest4

0.28

MutPred

0.53

.;.;Gain of catalytic residue at M94 (P = 2e-04);Gain of catalytic residue at M94 (P = 2e-04);Gain of catalytic residue at M94 (P = 2e-04);

MVP

0.91

MPC

0.42

ClinPred

0.71

GERP RS

5.1

Varity_R

0.50

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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