rs193061079

Variant names:

• chr19-42402003-C-T
• rs193061079
• NM_005357.4:c.3040G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005357.4(LIPE):​c.3040G>A​(p.Val1014Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,550,384 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: LIPE NM_005357.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3 B:1
• Conservation: PhyloP100: 3.02
• Publications: 3 publications found

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)

LOC101930071 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010096103).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005357.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPE	NM_005357.4	MANE Select	c.3040G>A	p.Val1014Met	missense	Exon 10 of 10	NP_005348.2
	LIPE	NM_001416100.1		c.2290G>A	p.Val764Met	missense	Exon 10 of 10	NP_001403029.1
	LIPE	NM_001416101.1		c.2275G>A	p.Val759Met	missense	Exon 10 of 10	NP_001403030.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPE	ENST00000244289.9	TSL:1 MANE Select	c.3040G>A	p.Val1014Met	missense	Exon 10 of 10	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4779C>T		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.3064G>A	p.Val1022Met	missense	Exon 10 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

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: 0.000478

GnomAD2 exomes AF: 0.000899 AC: 130 AN: 144540 AF XY: 0.000682

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000482

GnomAD4 exome AF: 0.000141 AC: 197 AN: 1398046 Hom.: 1 Cov.: 36 AF XY: 0.000130 AC XY: 90 AN XY: 690132

African (AFR) AF: 0.0000321 AC: 1 AN: 31130

American (AMR) AF: 0.00489 AC: 176 AN: 35974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24940

East Asian (EAS) AF: 0.00 AC: 0 AN: 35804

South Asian (SAS) AF: 0.00 AC: 0 AN: 79100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4788

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1081728

Other (OTH) AF: 0.000311 AC: 18 AN: 57936

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22 AN XY: 74496

African (AFR) AF: 0.0000722 AC: 3 AN: 41570

American (AMR) AF: 0.00242 AC: 37 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.000548

ExAC AF: 0.000265 AC: 29

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	-	1	LIPE-related disorder (1)
-	1	-	LIPE-related familial partial lipodystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.51
MVP		0.72
MPC		1.0
ClinPred		0.19	T
GERP RS		4.9
Varity_R		0.50
gMVP		0.75
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs193061079; hg19: chr19-42906155;