NM_006033.4:c.217C>A

Variant names:

• chr18-49565436-C-A
• NM_006033.4:c.217C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006033.4(LIPG):​c.217C>A​(p.Pro73Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LIPG NM_006033.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048110694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPG	NM_006033.4	c.217C>A	p.Pro73Thr	missense_variant	Exon 2 of 10	ENST00000261292.9	NP_006024.1
LIPG	NM_001308006.2	c.217C>A	p.Pro73Thr	missense_variant	Exon 2 of 9		NP_001294935.1
LIPG	XM_047437944.1	c.325C>A	p.Pro109Thr	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.217C>A	p.Pro73Thr	missense_variant	Exon 2 of 10	1	NM_006033.4	ENSP00000261292.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727248

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	3.3
DANN	Benign	0.70
DEOGEN2	Benign	0.25	T;T;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.58	T;T;T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.048	T;T;T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	-0.51	.;N;.;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	2.4	.;N;N;.
REVEL	Benign	0.20
Sift	Benign	1.0	.;T;T;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.067, 0.13	.;B;B;B
Vest4		0.13
MutPred		0.42		.;Gain of catalytic residue at P73 (P = 0.0596);Gain of catalytic residue at P73 (P = 0.0596);Gain of catalytic residue at P73 (P = 0.0596);
MVP		0.73
MPC		0.46
ClinPred		0.11	T
GERP RS		2.6
Varity_R		0.095
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-47091806;