18-49567494-C-G

Position:

• chr18-49567494-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006033.4(LIPG):​c.332C>G​(p.Thr111Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T111I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIPG NM_006033.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.421

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21114454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPG	NM_006033.4	c.332C>G	p.Thr111Arg	missense_variant	3/10	ENST00000261292.9
LIPG	NM_001308006.2	c.332C>G	p.Thr111Arg	missense_variant	3/9
LIPG	XM_047437944.1	c.440C>G	p.Thr147Arg	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPG	ENST00000261292.9	c.332C>G	p.Thr111Arg	missense_variant	3/10	1	NM_006033.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	1.3
DANN	Benign	0.87
DEOGEN2	Benign	0.26	T;T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.82	T;T;D;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.43	.;N;.;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.14	.;N;N;.
REVEL	Uncertain	0.31
Sift	Benign	0.17	.;T;D;.
Sift4G	Benign	0.53	T;T;T;T
Polyphen		0.0030, 0.055, 0.0020	.;B;B;B
Vest4		0.28
MutPred		0.41		.;Gain of MoRF binding (P = 0.0854);Gain of MoRF binding (P = 0.0854);Gain of MoRF binding (P = 0.0854);
MVP		0.88
MPC		0.41
ClinPred		0.076	T
GERP RS		-3.6
Varity_R		0.045
gMVP		0.31

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: rs2000813; hg19: chr18-47093864;