Variant 3-185511644-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139248.3(LIPH):c.1148A>G(p.Asn383Ser) 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 1,461,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LIPH
NM_139248.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.789

Variant links:

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]

LIPH links:

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ACMG classification

Classification made for transcript

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=0.11435494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPH	NM_139248.3 link	c.1148A>G	p.Asn383Ser	missense_variant	9/10	ENST00000296252.9	NP_640341.1	Q8WWY8
LIPH	XM_006713529.5 link	c.1058A>G	p.Asn353Ser	missense_variant	8/9		XP_006713592.1
LIPH	XM_017005852.3 link	c.1046A>G	p.Asn349Ser	missense_variant	8/9		XP_016861341.1	A2IBA6
LIPH	XM_011512530.4 link	c.1019A>G	p.Asn340Ser	missense_variant	10/11		XP_011510832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LIPH	ENST00000296252.9 link	c.1148A>G	p.Asn383Ser	missense_variant	9/10	1	NM_139248.3	ENSP00000296252.4	Q8WWY8
LIPH	ENST00000424591.6 link	c.1046A>G	p.Asn349Ser	missense_variant	8/9	1		ENSP00000396384.2	A2IBA6
LIPH	ENST00000435679.1 link	c.126-48A>G		intron_variant		5		ENSP00000390228.1	H7BZL3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.1148A>G (p.N383S) alteration is located in exon 9 (coding exon 9) of the LIPH gene. This alteration results from a A to G substitution at nucleotide position 1148, causing the asparagine (N) at amino acid position 383 to be replaced by a serine (S). 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

0.062

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.97

L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.24

Sift

Benign

0.39

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0010

B;B

Vest4

0.089

MutPred

0.51

Gain of sheet (P = 0.039);.;

MVP

0.89

MPC

0.096

ClinPred

0.11

GERP RS

2.6

Varity_R

0.054

gMVP

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over