Genetic Variant NM_005357.4:c.3203T>C (chr19-42401840-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_005357.4(LIPE):c.3203T>C(p.Val1068Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000764 in 1,309,744 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

LIPE
NM_005357.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.338

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=0.062469393).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPE	NM_005357.4 link	c.3203T>C	p.Val1068Ala	missense_variant	Exon 10 of 10	ENST00000244289.9	NP_005348.2	Q05469-1A8K8W7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPE	ENST00000244289.9 link	c.3203T>C	p.Val1068Ala	missense_variant	Exon 10 of 10	1	NM_005357.4	ENSP00000244289.3		Q05469-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.64e-7

AC:

AN:

1309744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

643632

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000254

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.0

DANN

Benign

0.49

DEOGEN2

Benign

0.042

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.23

M_CAP

Benign

0.0011

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.18

REVEL

Benign

0.045

Sift

Benign

0.058

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.093

MutPred

0.13

Gain of loop (P = 0.1069);

MVP

0.18

MPC

0.37

ClinPred

0.21

GERP RS

1.9

Varity_R

0.024

gMVP

0.20

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over