chr19-42402015-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005357.4(LIPE):ā€‹c.3028C>Gā€‹(p.Leu1010Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,391,242 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 (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000029 ( 0 hom. )

Consequence

LIPE
NM_005357.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.950
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-AS1 (HGNC:48589): (LIPE antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19030795).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LIPENM_005357.4 linkuse as main transcriptc.3028C>G p.Leu1010Val missense_variant 10/10 ENST00000244289.9
LIPE-AS1NR_073180.1 linkuse as main transcriptn.77+4791G>C intron_variant, non_coding_transcript_variant
LOC101930071NR_126041.1 linkuse as main transcriptn.97+4791G>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LIPEENST00000244289.9 linkuse as main transcriptc.3028C>G p.Leu1010Val missense_variant 10/101 NM_005357.4 P1Q05469-1
LIPE-AS1ENST00000594624.7 linkuse as main transcriptn.66+4791G>C intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000726
AC:
1
AN:
137742
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
75366
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000418
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000288
AC:
4
AN:
1391242
Hom.:
0
Cov.:
36
AF XY:
0.00
AC XY:
0
AN XY:
685998
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000283
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000567
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.28e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsJan 25, 2023The c.3028C>G (p.L1010V) alteration is located in exon 10 (coding exon 10) of the LIPE gene. This alteration results from a C to G substitution at nucleotide position 3028, causing the leucine (L) at amino acid position 1010 to be replaced by a valine (V). 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
0.075
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
18
DANN
Benign
0.96
DEOGEN2
Benign
0.097
T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.44
N
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.77
N
MutationTaster
Benign
0.97
N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.075
Sift
Benign
0.13
T
Sift4G
Uncertain
0.028
D
Polyphen
0.78
P
Vest4
0.14
MutPred
0.54
Gain of MoRF binding (P = 0.084);
MVP
0.56
MPC
0.53
ClinPred
0.12
T
GERP RS
1.3
Varity_R
0.084
gMVP
0.24

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.

Other links and lift over

dbSNP: rs1308856793; hg19: chr19-42906167; API