chr19-42401852-C-G

Variant names:

• chr19-42401852-C-G
• rs572063779
• NM_005357.4:c.3191G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005357.4(LIPE):​c.3191G>C​(p.Gly1064Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000854 in 1,523,090 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. G1064E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000080 (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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.011962652).

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>C	p.Gly1064Ala	missense	Exon 10 of 10	NP_005348.2
	LIPE	NM_001416100.1		c.2441G>C	p.Gly814Ala	missense	Exon 10 of 10	NP_001403029.1
	LIPE	NM_001416101.1		c.2426G>C	p.Gly809Ala	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>C	p.Gly1064Ala	missense	Exon 10 of 10	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4628C>G		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.3215G>C	p.Gly1072Ala	missense	Exon 10 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152186 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: 0.000386

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: 0.0000304

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000343

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000285

GnomAD4 exome AF: 0.00000802 AC: 11 AN: 1370904 Hom.: 0 Cov.: 34 AF XY: 0.00000887 AC XY: 6 AN XY: 676154

African (AFR) AF: 0.00 AC: 0 AN: 29544

American (AMR) AF: 0.00 AC: 0 AN: 33568

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

East Asian (EAS) AF: 0.000146 AC: 5 AN: 34220

South Asian (SAS) AF: 0.0000261 AC: 2 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: 1071256

Other (OTH) AF: 0.0000702 AC: 4 AN: 56984

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152186 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15288

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

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

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

Alfa AF: 0.0000436 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.0000432 AC: 4

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	0.064
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.4
DANN	Benign	0.72
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.0080
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.015
Sift	Benign	0.12	T
Sift4G	Benign	1.0	T
Polyphen		0.025	B
Vest4		0.098
MutPred		0.13		Gain of helix (P = 0.0496)
MVP		0.43
MPC		0.33
ClinPred		0.021	T
GERP RS		1.8
Varity_R		0.028
gMVP		0.15
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;