Variant 10-88726796-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001080518.2(LIPK):c.107G>A(p.Ser36Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,485,516 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 14 hom. )

Consequence

LIPK
NM_001080518.2 missense, splice_region

Scores

Splicing: ADA: 0.9850

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.15

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 -6 ACMG points.

BP6

Variant 10-88726796-G-A is Benign according to our data. Variant chr10-88726796-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3043954.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPK	NM_001080518.2 linkuse as main transcript	c.107G>A	p.Ser36Asn	missense_variant, splice_region_variant	3/10	ENST00000404190.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPK	ENST00000404190.3 linkuse as main transcript	c.107G>A	p.Ser36Asn	missense_variant, splice_region_variant	3/10	1	NM_001080518.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

352

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.0407

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00354

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00228

AC:

530

AN:

232388

Hom.:

AF XY:

0.00221

AC XY:

277

AN XY:

125286

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000906

Gnomad ASJ exome

AF:

0.00271

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.000665

Gnomad NFE exome

AF:

0.00365

Gnomad OTH exome

AF:

0.00298

GnomAD4 exome

AF:

0.00325

AC:

4339

AN:

1333230

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

2147

AN XY:

668612

show subpopulations

Gnomad4 AFR exome

AF:

0.000808

Gnomad4 AMR exome

AF:

0.00104

Gnomad4 ASJ exome

AF:

0.00274

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00189

Gnomad4 FIN exome

AF:

0.000963

Gnomad4 NFE exome

AF:

0.00384

Gnomad4 OTH exome

AF:

0.00280

GnomAD4 genome

AF:

0.00231

AC:

352

AN:

152286

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

159

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00354

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00329

Hom.:

Bravo

AF:

0.00249

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00138

AC:

ESP6500EA

AF:

0.00392

AC:

ExAC

AF:

0.00218

AC:

263

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

LIPK-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 30, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.78

M_CAP

Benign

0.043

MetaRNN

Benign

0.013

MetaSVM

Uncertain

0.72

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

0.52

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.42

Sift

Uncertain

0.026

Sift4G

Uncertain

0.017

Polyphen

0.96

Vest4

0.28

MVP

0.92

MPC

0.030

ClinPred

0.032

GERP RS

5.2

Varity_R

0.30

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.87

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