Variant 19-42401852-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005357.4(LIPE):c.3191G>C(p.Gly1064Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000854 in 1,523,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000080 ( 0 hom. )

Consequence

LIPE
NM_005357.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00800

Variant links:

Genes affected

LIPE (HGNC:6621): (lipase E, hormone sensitive type) The protein encoded by this gene has a long and a short form, generated by use of alternative translational start codons. The long form is expressed in steroidogenic tissues such as testis, where it converts cholesteryl esters to free cholesterol for steroid hormone production. The short form is expressed in adipose tissue, among others, where it hydrolyzes stored triglycerides to free fatty acids. [provided by RefSeq, Jul 2008]

LIPE links:

LIPE-AS1 (HGNC:48589): (LIPE antisense RNA 1)

LIPE-AS1 links:

LOC101930071 (HGNC:):

LOC101930071 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011962652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LIPE	NM_005357.4 linkuse as main transcript	c.3191G>C	p.Gly1064Ala	missense_variant	10/10	ENST00000244289.9	NP_005348.2
LIPE-AS1	NR_073180.1 linkuse as main transcript	n.77+4628C>G		intron_variant, non_coding_transcript_variant
LOC101930071	NR_126041.1 linkuse as main transcript	n.97+4628C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPE	ENST00000244289.9 linkuse as main transcript	c.3191G>C	p.Gly1064Ala	missense_variant	10/10	1	NM_005357.4	ENSP00000244289	P1	Q05469-1
LIPE-AS1	ENST00000594624.7 linkuse as main transcript	n.66+4628C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000336

AC:

AN:

119176

Hom.:

AF XY:

0.0000304

AC XY:

AN XY:

65688

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000343

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000285

GnomAD4 exome

AF:

0.00000802

AC:

AN:

1370904

Hom.:

Cov.:

AF XY:

0.00000887

AC XY:

AN XY:

676154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000146

Gnomad4 SAS exome

AF:

0.0000261

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000702

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000436

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000432

AC:

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

Dec 05, 2022

The c.3191G>C (p.G1064A) alteration is located in exon 10 (coding exon 10) of the LIPE gene. This alteration results from a G to C substitution at nucleotide position 3191, causing the glycine (G) at amino acid position 1064 to be replaced by an alanine (A). 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

0.064

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.4

DANN

Benign

0.72

DEOGEN2

Benign

0.038

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.36

M_CAP

Benign

0.0048

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.29

REVEL

Benign

0.015

Sift

Benign

0.12

Sift4G

Benign

1.0

Polyphen

0.025

Vest4

0.098

MutPred

0.13

Gain of helix (P = 0.0496);

MVP

0.43

MPC

0.33

ClinPred

0.021

GERP RS

1.8

Varity_R

0.028

gMVP

0.15

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