19-42402068-G-A

Variant names:

• chr19-42402068-G-A
• rs2039992647
• NM_005357.4:c.2975C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005357.4(LIPE):​c.2975C>T​(p.Ala992Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000748 in 1,337,464 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: LIPE NM_005357.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94
• 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.

• PM2: Very rare variant in population databases, with high coverage

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.2975C>T	p.Ala992Val	missense	Exon 10 of 10	NP_005348.2
	LIPE	NM_001416100.1		c.2225C>T	p.Ala742Val	missense	Exon 10 of 10	NP_001403029.1
	LIPE	NM_001416101.1		c.2210C>T	p.Ala737Val	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.2975C>T	p.Ala992Val	missense	Exon 10 of 10	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4844G>A		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.2999C>T	p.Ala1000Val	missense	Exon 10 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.48e-7 AC: 1 AN: 1337464 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 653570

African (AFR) AF: 0.00 AC: 0 AN: 27960

American (AMR) AF: 0.00 AC: 0 AN: 29996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21606

East Asian (EAS) AF: 0.00 AC: 0 AN: 32634

South Asian (SAS) AF: 0.00 AC: 0 AN: 70356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4410

European-Non Finnish (NFE) AF: 9.53e-7 AC: 1 AN: 1049222

Other (OTH) AF: 0.00 AC: 0 AN: 55292

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Uncertain	0.46
BayesDel_addAF	Benign	0.0068	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.082	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.9
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.26
Sift	Benign	0.20	T
Sift4G	Benign	0.25	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.62		Gain of sheet (P = 0.1945)
MVP		0.84
MPC		0.99
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.16
gMVP		0.64
Mutation Taster		=54/46	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: rs2039992647; hg19: chr19-42906220;