chr18-49565473-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_006033.4(LIPG):​c.254C>T​(p.Thr85Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

LIPG
NM_006033.4 missense

Scores

6
11
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.90
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.96

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LIPGNM_006033.4 linkc.254C>T p.Thr85Ile missense_variant Exon 2 of 10 ENST00000261292.9 NP_006024.1 Q9Y5X9-1A0A024R2B5
LIPGNM_001308006.2 linkc.254C>T p.Thr85Ile missense_variant Exon 2 of 9 NP_001294935.1 Q9Y5X9B4DTR8
LIPGXM_047437944.1 linkc.362C>T p.Thr121Ile missense_variant Exon 2 of 5 XP_047293900.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LIPGENST00000261292.9 linkc.254C>T p.Thr85Ile missense_variant Exon 2 of 10 1 NM_006033.4 ENSP00000261292.4 Q9Y5X9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 24, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.254C>T (p.T85I) alteration is located in exon 2 (coding exon 2) of the LIPG gene. This alteration results from a C to T substitution at nucleotide position 254, causing the threonine (T) at amino acid position 85 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Pathogenic
0.42
D
BayesDel_noAF
Pathogenic
0.36
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.64
D;.;D;D;.
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.96
D;T;D;D;D
M_CAP
Pathogenic
0.36
D
MetaRNN
Pathogenic
0.96
D;D;D;D;D
MetaSVM
Pathogenic
0.80
D
MutationAssessor
Uncertain
2.5
.;.;M;.;M
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-3.6
.;.;D;D;.
REVEL
Pathogenic
0.89
Sift
Benign
0.031
.;.;D;D;.
Sift4G
Uncertain
0.013
D;D;T;T;D
Polyphen
0.98, 0.99
.;.;D;D;D
Vest4
0.92
MutPred
0.85
.;.;Gain of ubiquitination at K84 (P = 0.0543);Gain of ubiquitination at K84 (P = 0.0543);Gain of ubiquitination at K84 (P = 0.0543);
MVP
0.99
MPC
1.1
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.64
gMVP
0.78

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2084594724; hg19: chr18-47091843; API