Variant 10-88740051-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001080518.2(LIPK):c.872T>G(p.Met291Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,604,976 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 2 hom. )

Consequence

LIPK
NM_001080518.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.26

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 -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.771

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPK	NM_001080518.2 linkuse as main transcript	c.872T>G	p.Met291Arg	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.872T>G	p.Met291Arg	missense_variant	8/10	1	NM_001080518.2	ENSP00000383900	P1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000350

AC:

AN:

248736

Hom.:

AF XY:

0.000459

AC XY:

AN XY:

134960

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000452

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000545

AC:

792

AN:

1453018

Hom.:

Cov.:

AF XY:

0.000552

AC XY:

399

AN XY:

723012

show subpopulations

Gnomad4 AFR exome

AF:

0.0000904

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000872

Gnomad4 FIN exome

AF:

0.0000573

Gnomad4 NFE exome

AF:

0.000616

Gnomad4 OTH exome

AF:

0.000485

GnomAD4 genome

AF:

0.000237

AC:

AN:

151958

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000431

Hom.:

Bravo

AF:

0.000253

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000252

AC:

ESP6500EA

AF:

0.000357

AC:

ExAC

AF:

0.000372

AC:

EpiCase

AF:

0.000328

EpiControl

AF:

0.000178

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

Jun 21, 2021

The c.872T>G (p.M291R) alteration is located in exon 7 (coding exon 7) of the LIPK gene. This alteration results from a T to G substitution at nucleotide position 872, causing the methionine (M) at amino acid position 291 to be replaced by an arginine (R). 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

Pathogenic

0.76

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.083

MetaRNN

Pathogenic

0.77

MetaSVM

Uncertain

0.37

MutationAssessor

Pathogenic

3.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.8

REVEL

Pathogenic

0.78

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.99

Vest4

0.91

MVP

0.70

MPC

0.031

ClinPred

0.36

GERP RS

5.4

Varity_R

0.98

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.35

Position offset: 16

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