19-42401840-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005357.4(LIPE):ā€‹c.3203T>Gā€‹(p.Val1068Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,453,816 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 Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.000014 ( 0 hom., cov: 31)
Exomes š‘“: 0.000012 ( 0 hom. )

Consequence

LIPE
NM_005357.4 missense

Scores

1
2
16

Clinical Significance

Likely benign criteria provided, single submitter B:1

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

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.055652052).
BP6
Variant 19-42401840-A-C is Benign according to our data. Variant chr19-42401840-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3119054.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LIPENM_005357.4 linkuse as main transcriptc.3203T>G p.Val1068Gly missense_variant 10/10 ENST00000244289.9
LIPE-AS1NR_073180.1 linkuse as main transcriptn.77+4616A>C intron_variant, non_coding_transcript_variant
LOC101930071NR_126041.1 linkuse as main transcriptn.97+4616A>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.3203T>G p.Val1068Gly missense_variant 10/101 NM_005357.4 P1Q05469-1
LIPE-AS1ENST00000594624.7 linkuse as main transcriptn.66+4616A>C intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.0000139
AC:
2
AN:
144086
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000521
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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:
0.0000114
AC:
1
AN:
87748
Hom.:
0
AF XY:
0.0000202
AC XY:
1
AN XY:
49448
show subpopulations
Gnomad AFR exome
AF:
0.000325
Gnomad AMR exome
AF:
0.00
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:
0.0000122
AC:
16
AN:
1309730
Hom.:
0
Cov.:
32
AF XY:
0.0000109
AC XY:
7
AN XY:
643628
show subpopulations
Gnomad4 AFR exome
AF:
0.000185
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:
0.00
Gnomad4 NFE exome
AF:
0.00000965
Gnomad4 OTH exome
AF:
0.0000185
GnomAD4 genome
AF:
0.0000139
AC:
2
AN:
144086
Hom.:
0
Cov.:
31
AF XY:
0.0000143
AC XY:
1
AN XY:
69938
show subpopulations
Gnomad4 AFR
AF:
0.0000521
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJan 04, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.048
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
9.5
DANN
Benign
0.75
DEOGEN2
Benign
0.059
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0051
N
LIST_S2
Benign
0.15
T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.056
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.46
N
REVEL
Benign
0.058
Sift
Uncertain
0.0040
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.0
B
Vest4
0.079
MutPred
0.24
Loss of stability (P = 0.014);
MVP
0.28
MPC
0.40
ClinPred
0.13
T
GERP RS
1.9
Varity_R
0.060
gMVP
0.28

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: rs1367745104; hg19: chr19-42905992; API