19-42401821-CCCCCCGCAGCCCCCGTCTA-CCCCCCGCAGCCCCCGTCTACCCCCGCAGCCCCCGTCTACCCCCGCAGCCCCCGTCTACCCCCGCAGCCCCCGTCTA

Variant names:

• chr19-42401821-C-CCCCCCGCAGCCCCCGTCTACCCCCGCAGCCCCCGTCTACCCCCGCAGCCCCCGTCTA
• NM_005357.4:c.3221_3222insTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGG

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_005357.4(LIPE):​c.3221_3222insTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGG​(p.Gly1074_Arg1075insArgArgGlyLeuArgGlyTerThrGlyAlaAlaGlyValAspGlyGlyCysGlyGly) variant causes a stop gained, disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000753 in 1,328,364 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: LIPE NM_005357.4 stop_gained, disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0031 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• 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.3221_3222insTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGG	p.Gly1074_Arg1075insArgArgGlyLeuArgGlyTerThrGlyAlaAlaGlyValAspGlyGlyCysGlyGly	stop_gained, disruptive_inframe_insertion	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.3221_3222insTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGG	p.Gly1074_Arg1075insArgArgGlyLeuArgGlyTerThrGlyAlaAlaGlyValAspGlyGlyCysGlyGly	stop_gained, disruptive_inframe_insertion	Exon 10 of 10	1	NM_005357.4	ENSP00000244289.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.53e-7 AC: 1 AN: 1328364 Hom.: 0 Cov.: 30 AF XY: 0.00000153 AC XY: 1 AN XY: 652630

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: 0.00

Gnomad4 OTH exome AF: 0.0000181

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-42905973;