19-42401855-G-A

Variant names:

• chr19-42401855-G-A
• rs745859081
• NM_005357.4:c.3188C>T

Variant summary

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

The NM_005357.4(LIPE):​c.3188C>T​(p.Thr1063Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 439,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1063R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000030 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: LIPE NM_005357.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029404163).

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.3188C>T	p.Thr1063Met	missense	Exon 10 of 10	NP_005348.2
	LIPE	NM_001416100.1		c.2438C>T	p.Thr813Met	missense	Exon 10 of 10	NP_001403029.1
	LIPE	NM_001416101.1		c.2423C>T	p.Thr808Met	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.3188C>T	p.Thr1063Met	missense	Exon 10 of 10	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4631G>A		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.3212C>T	p.Thr1071Met	missense	Exon 10 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes AF: 0.0000304 AC: 4 AN: 131374 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: 0.000597

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000329

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000924 AC: 8 AN: 86586 AF XY: 0.000121

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000130 AC: 40 AN: 308564 Hom.: 0 Cov.: 7 AF XY: 0.000196 AC XY: 32 AN XY: 163034

African (AFR) AF: 0.00 AC: 0 AN: 6154

American (AMR) AF: 0.00 AC: 0 AN: 13768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8120

East Asian (EAS) AF: 0.00 AC: 0 AN: 5360

South Asian (SAS) AF: 0.000820 AC: 35 AN: 42668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1068

European-Non Finnish (NFE) AF: 0.00000985 AC: 2 AN: 203114

Other (OTH) AF: 0.000232 AC: 3 AN: 12926

GnomAD4 genome AF: 0.0000304 AC: 4 AN: 131374 Hom.: 0 Cov.: 31 AF XY: 0.0000474 AC XY: 3 AN XY: 63322

African (AFR) AF: 0.00 AC: 0 AN: 36138

American (AMR) AF: 0.00 AC: 0 AN: 13324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3146

East Asian (EAS) AF: 0.00 AC: 0 AN: 3876

South Asian (SAS) AF: 0.000597 AC: 2 AN: 3350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.0000329 AC: 2 AN: 60812

Other (OTH) AF: 0.00 AC: 0 AN: 1814

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000638 AC: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.5
DANN	Uncertain	0.98
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.082
Sift	Benign	0.094	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.99	D
Vest4		0.14
MutPred		0.19		Loss of glycosylation at T1063 (P = 0.0134)
MVP		0.52
MPC		0.32
ClinPred		0.14	T
GERP RS		-0.64
Varity_R		0.023
gMVP		0.27
Mutation Taster		=98/2	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: rs745859081; hg19: chr19-42906007;