18-49567490-C-T

Position:

• chr18-49567490-C-T

Variant summary

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

The NM_006033.4(LIPG):​c.328C>T​(p.His110Tyr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LIPG NM_006033.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72

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=0.19964561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPG	NM_006033.4	c.328C>T	p.His110Tyr	missense_variant	3/10	ENST00000261292.9	NP_006024.1
LIPG	NM_001308006.2	c.328C>T	p.His110Tyr	missense_variant	3/9		NP_001294935.1
LIPG	XM_047437944.1	c.436C>T	p.His146Tyr	missense_variant	3/5		XP_047293900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPG	ENST00000261292.9	c.328C>T	p.His110Tyr	missense_variant	3/10	1	NM_006033.4	ENSP00000261292.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2023

The c.328C>T (p.H110Y) alteration is located in exon 3 (coding exon 3) of the LIPG gene. This alteration results from a C to T substitution at nucleotide position 328, causing the histidine (H) at amino acid position 110 to be replaced by a tyrosine (Y). 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	Benign	0.073
BayesDel_addAF	Benign	0.00020	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	15
DANN	Benign	0.76
DEOGEN2	Benign	0.26	T;T;T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T;T;D;T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	-1.4	.;N;.;N
MutationTaster	Benign	0.99	N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.94	.;N;N;.
REVEL	Uncertain	0.31
Sift	Benign	0.33	.;T;T;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.16, 0.26, 0.13	.;B;B;B
Vest4		0.14
MutPred		0.51		.;Loss of disorder (P = 0.0402);Loss of disorder (P = 0.0402);Loss of disorder (P = 0.0402);
MVP		0.91
MPC		0.56
ClinPred		0.63	D
GERP RS		5.1
Varity_R		0.11
gMVP		0.44

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: rs1426284437; hg19: chr18-47093860;