chr19-42401831-C-G

Variant names:

• chr19-42401831-C-G
• rs751898723
• NM_005357.4:c.3212G>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.3212G>C​(p.Gly1071Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,328,518 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. G1071D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: LIPE NM_005357.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.671
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04872611).

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.3212G>C	p.Gly1071Ala	missense	Exon 10 of 10	NP_005348.2
	LIPE	NM_001416100.1		c.2462G>C	p.Gly821Ala	missense	Exon 10 of 10	NP_001403029.1
	LIPE	NM_001416101.1		c.2447G>C	p.Gly816Ala	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.3212G>C	p.Gly1071Ala	missense	Exon 10 of 10	ENSP00000244289.3	Q05469-1
	LIPE-AS1	ENST00000594624.8	TSL:1	n.105+4607C>G		intron	N/A
	LIPE	ENST00000599918.2	TSL:5	c.3236G>C	p.Gly1079Ala	missense	Exon 10 of 10	ENSP00000472218.2	M0R201

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000116 AC: 1 AN: 86092 AF XY: 0.00

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: 0.00000151 AC: 2 AN: 1328518 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 653458

African (AFR) AF: 0.00 AC: 0 AN: 27588

American (AMR) AF: 0.00 AC: 0 AN: 26206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21628

East Asian (EAS) AF: 0.00 AC: 0 AN: 32756

South Asian (SAS) AF: 0.0000283 AC: 2 AN: 70782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3818

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1050692

Other (OTH) AF: 0.00 AC: 0 AN: 55092

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	LIPE-related familial partial lipodystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.86
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.67
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.022
Sift	Benign	0.45	T
Polyphen		0.092	B
Vest4		0.036
MutPred		0.19		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.29
MPC		0.33
ClinPred		0.034	T
GERP RS		-0.016
Varity_R		0.035
gMVP		0.25
Mutation Taster		=100/0	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: rs751898723; hg19: chr19-42905983;