Variant 10-88740016-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001080518.2(LIPK):c.837G>T(p.Leu279Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.000034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LIPK
NM_001080518.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.28

Variant links:

Genes affected

LIPK (HGNC:23444): (lipase family member K) Predicted to enable lipoprotein lipase activity. Predicted to be involved in cornification. Predicted to be located in extracellular region. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LIPK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07865685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPK	NM_001080518.2 linkuse as main transcript	c.837G>T	p.Leu279Phe	missense_variant	8/10	ENST00000404190.3	NP_001073987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPK	ENST00000404190.3 linkuse as main transcript	c.837G>T	p.Leu279Phe	missense_variant	8/10	1	NM_001080518.2	ENSP00000383900	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148334

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000492

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000437

Gnomad SAS

AF:

0.000242

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00232

AC:

2708

AN:

1168652

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

1325

AN XY:

586534

show subpopulations

Gnomad4 AFR exome

AF:

0.00315

Gnomad4 AMR exome

AF:

0.00216

Gnomad4 ASJ exome

AF:

0.00465

Gnomad4 EAS exome

AF:

0.00379

Gnomad4 SAS exome

AF:

0.000294

Gnomad4 FIN exome

AF:

0.00641

Gnomad4 NFE exome

AF:

0.00211

Gnomad4 OTH exome

AF:

0.00385

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000337

AC:

AN:

148484

Hom.:

Cov.:

AF XY:

0.0000414

AC XY:

AN XY:

72526

show subpopulations

Gnomad4 AFR

AF:

0.0000491

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000438

Gnomad4 SAS

AF:

0.000241

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 15, 2021

The c.837G>T (p.L279F) alteration is located in exon 7 (coding exon 7) of the LIPK gene. This alteration results from a G to T substitution at nucleotide position 837, causing the leucine (L) at amino acid position 279 to be replaced by a phenylalanine (F). 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

0.18

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0052

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.064

M_CAP

Benign

0.018

MetaRNN

Benign

0.079

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.3

REVEL

Benign

0.061

Sift

Benign

0.27

Sift4G

Benign

0.29

Polyphen

0.072

Vest4

0.17

MutPred

0.60

Gain of catalytic residue at L279 (P = 0.0547);

MVP

0.29

MPC

0.0078

ClinPred

0.17

GERP RS

1.4

Varity_R

0.056

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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