19-42402068-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPE	NM_005357.4	c.2975C>T	p.Ala992Val	missense_variant	Exon 10 of 10	ENST00000244289.9	NP_005348.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPE	ENST00000244289.9	c.2975C>T	p.Ala992Val	missense_variant	Exon 10 of 10	1	NM_005357.4	ENSP00000244289.3

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

Gnomad4 AFR exome AF: 0.00

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: 9.53e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Mar 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2975C>T (p.A992V) alteration is located in exon 10 (coding exon 10) of the LIPE gene. This alteration results from a C to T substitution at nucleotide position 2975, causing the alanine (A) at amino acid position 992 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Other links and lift over

dbSNP: rs2039992647; hg19: chr19-42906220;