18-49565424-G-T

Variant names:

• chr18-49565424-G-T
• rs202204825
• NM_006033.4:c.205G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006033.4(LIPG):​c.205G>T​(p.Gly69Cys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIPG NM_006033.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.04

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPG	NM_006033.4	c.205G>T	p.Gly69Cys	missense_variant	Exon 2 of 10	ENST00000261292.9	NP_006024.1
LIPG	NM_001308006.2	c.205G>T	p.Gly69Cys	missense_variant	Exon 2 of 9		NP_001294935.1
LIPG	XM_047437944.1	c.313G>T	p.Gly105Cys	missense_variant	Exon 2 of 5		XP_047293900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPG	ENST00000261292.9	c.205G>T	p.Gly69Cys	missense_variant	Exon 2 of 10	1	NM_006033.4	ENSP00000261292.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.74	D;D;D;.
Eigen	Benign	0.098
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T;T;T;T
M_CAP	Pathogenic	0.53	D
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Uncertain	0.53	D
MutationAssessor	Pathogenic	3.3	.;M;.;M
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-6.3	.;D;D;.
REVEL	Uncertain	0.58
Sift	Uncertain	0.0080	.;D;D;.
Sift4G	Uncertain	0.058	T;D;D;T
Polyphen		0.59, 0.74	.;P;P;P
Vest4		0.39
MutPred		0.62		.;Loss of disorder (P = 0.0512);Loss of disorder (P = 0.0512);Loss of disorder (P = 0.0512);
MVP		0.97
MPC		0.71
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.54
gMVP		0.72

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: rs202204825; hg19: chr18-47091794;