NM_006033.4:c.332C>G

Variant names:

• chr18-49567494-C-G
• rs2000813
• NM_006033.4:c.332C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• Publications: 109 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006033.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPG	NM_006033.4	MANE Select	c.332C>G	p.Thr111Arg	missense	Exon 3 of 10	NP_006024.1	Q9Y5X9-1
	LIPG	NM_001308006.2		c.332C>G	p.Thr111Arg	missense	Exon 3 of 9	NP_001294935.1	B4DTR8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPG	ENST00000261292.9	TSL:1 MANE Select	c.332C>G	p.Thr111Arg	missense	Exon 3 of 10	ENSP00000261292.4	Q9Y5X9-1
	LIPG	ENST00000580036.5	TSL:1	c.332C>G	p.Thr111Arg	missense	Exon 3 of 6	ENSP00000462420.1	Q9Y5X9-2
	LIPG	ENST00000959465.1		c.332C>G	p.Thr111Arg	missense	Exon 3 of 10	ENSP00000629524.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 30546

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.43	N
PhyloP100		0.42
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.14	N
REVEL	Uncertain	0.31
Sift	Benign	0.17	T
Sift4G	Benign	0.53	T
Polyphen		0.0030	B
Vest4		0.28
MutPred		0.41		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

Other links and lift over

dbSNP: rs2000813; hg19: chr18-47093864;