NM_005357.4:c.3191G>A

Variant names:

• chr19-42401852-C-T
• rs572063779
• NM_005357.4:c.3191G>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.3191G>A​(p.Gly1064Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000309 in 1,523,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1064A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: LIPE NM_005357.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00800
• Publications: 1 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=0.0071200132).

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.3191G>A	p.Gly1064Glu	missense	Exon 10 of 10	NP_005348.2
	LIPE	NM_001416100.1		c.2441G>A	p.Gly814Glu	missense	Exon 10 of 10	NP_001403029.1
	LIPE	NM_001416101.1		c.2426G>A	p.Gly809Glu	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.3191G>A	p.Gly1064Glu	missense	Exon 10 of 10	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4628C>T		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.3215G>A	p.Gly1072Glu	missense	Exon 10 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152186 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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

GnomAD2 exomes AF: 0.0000336 AC: 4 AN: 119176 AF XY: 0.00

Gnomad AFR exome AF: 0.000494

Gnomad AMR exome AF: 0.0000916

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: 0.00

GnomAD4 exome AF: 0.0000146 AC: 20 AN: 1370902 Hom.: 0 Cov.: 34 AF XY: 0.00000592 AC XY: 4 AN XY: 676152

African (AFR) AF: 0.000508 AC: 15 AN: 29544

American (AMR) AF: 0.0000596 AC: 2 AN: 33568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24092

East Asian (EAS) AF: 0.00 AC: 0 AN: 34220

South Asian (SAS) AF: 0.00 AC: 0 AN: 76688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4094

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071254

Other (OTH) AF: 0.0000526 AC: 3 AN: 56984

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152296 Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 12 AN XY: 74456

African (AFR) AF: 0.000577 AC: 24 AN: 41570

American (AMR) AF: 0.000196 AC: 3 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000272

ExAC AF: 0.000108 AC: 10

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	Benign	0.081
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.2
DANN	Benign	0.93
DEOGEN2	Benign	0.046	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.0071	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.0080
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.49	N
REVEL	Benign	0.015
Sift	Benign	0.12	T
Sift4G	Benign	0.41	T
Polyphen		0.030	B
Vest4		0.033
MutPred		0.17		Gain of solvent accessibility (P = 0.0411)
MVP		0.45
MPC		0.40
ClinPred		0.017	T
GERP RS		1.8
Varity_R		0.027
gMVP		0.16
Mutation Taster		=99/1	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: rs572063779; hg19: chr19-42906004;