NM_005357.4:c.2984C>T

Variant names:

• chr19-42402059-G-A
• rs1008817231
• NM_005357.4:c.2984C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_005357.4(LIPE):​c.2984C>T​(p.Pro995Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000127 in 1,504,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P995P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: LIPE NM_005357.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.18
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.908

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.2984C>T	p.Pro995Leu	missense	Exon 10 of 10	NP_005348.2
	LIPE	NM_001416100.1		c.2234C>T	p.Pro745Leu	missense	Exon 10 of 10	NP_001403029.1
	LIPE	NM_001416101.1		c.2219C>T	p.Pro740Leu	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.2984C>T	p.Pro995Leu	missense	Exon 10 of 10	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4835G>A		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.3008C>T	p.Pro1003Leu	missense	Exon 10 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152252 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000276 AC: 3 AN: 108694 AF XY: 0.0000341

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000761

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000136 AC: 184 AN: 1352144 Hom.: 0 Cov.: 36 AF XY: 0.000127 AC XY: 84 AN XY: 662218

African (AFR) AF: 0.00 AC: 0 AN: 28798

American (AMR) AF: 0.00 AC: 0 AN: 31748

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22506

East Asian (EAS) AF: 0.00 AC: 0 AN: 33414

South Asian (SAS) AF: 0.00 AC: 0 AN: 72378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4480

European-Non Finnish (NFE) AF: 0.000162 AC: 171 AN: 1056480

Other (OTH) AF: 0.000232 AC: 13 AN: 55932

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152252 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74388

African (AFR) AF: 0.00 AC: 0 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000121 Hom.: 0

Bravo AF: 0.0000793

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.2
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.75		Loss of disorder (P = 0.1232)
MVP		0.78
MPC		0.59
ClinPred		0.69	D
GERP RS		4.9
Varity_R		0.70
gMVP		0.85
Mutation Taster		=19/81	disease causing

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: rs1008817231; hg19: chr19-42906211;