chr3-185514507-C-G

Variant names:

• chr3-185514507-C-G
• rs748571081
• NM_139248.3:c.997G>C

Variant summary

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

The NM_139248.3(LIPH):​c.997G>C​(p.Val333Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIPH NM_139248.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

Genes affected

LIPH (HGNC:18483): (lipase H) This gene encodes a membrane-bound member of the mammalian triglyceride lipase family. It catalyzes the production of 2-acyl lysophosphatidic acid (LPA), which is a lipid mediator with diverse biological properties that include platelet aggregation, smooth muscle contraction, and stimulation of cell proliferation and motility. [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=0.1848863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPH	NM_139248.3	c.997G>C	p.Val333Leu	missense_variant	Exon 8 of 10	ENST00000296252.9	NP_640341.1
LIPH	XM_006713529.5	c.907G>C	p.Val303Leu	missense_variant	Exon 7 of 9		XP_006713592.1
LIPH	XM_017005852.3	c.895G>C	p.Val299Leu	missense_variant	Exon 7 of 9		XP_016861341.1
LIPH	XM_011512530.4	c.868G>C	p.Val290Leu	missense_variant	Exon 9 of 11		XP_011510832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPH	ENST00000296252.9	c.997G>C	p.Val333Leu	missense_variant	Exon 8 of 10	1	NM_139248.3	ENSP00000296252.4
LIPH	ENST00000424591.6	c.895G>C	p.Val299Leu	missense_variant	Exon 7 of 9	1		ENSP00000396384.2
LIPH	ENST00000435679.1	c.28G>C	p.Val10Leu	missense_variant	Exon 2 of 4	5		ENSP00000390228.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 19

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.84	T;D
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.54	N;N
REVEL	Benign	0.28
Sift	Benign	0.73	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.0010	B;B
Vest4		0.33
MutPred		0.57		Loss of MoRF binding (P = 0.1392);.;
MVP		0.78
MPC		0.13
ClinPred		0.24	T
GERP RS		4.0
Varity_R		0.13
gMVP		0.78

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: rs748571081; hg19: chr3-185232295;