19-42401821-CCCCCCGCAGCCCCCGTCTA-CCCCCCGCAGCCCCCGTCTACCCCCGCAGCCCCCGTCTACCCCCGCAGCCCCCGTCTA

Variant names:

• chr19-42401821-C-CCCCCCGCAGCCCCCGTCTACCCCCGCAGCCCCCGTCTA
• NM_005357.4:c.3221_3222insTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_005357.4(LIPE):​c.3221_3222insTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGG​(p.His1076ArgfsTer6) variant causes a frameshift, stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,328,322 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: 𝑓 0.000039 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIPE NM_005357.4 frameshift, stop_gained
• 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 2 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPE	NM_005357.4	c.3221_3222insTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGG	p.His1076ArgfsTer6	frameshift_variant, stop_gained	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_3222insTAGACGGGGGCTGCGGGGGTAGACGGGGGCTGCGGGGG	p.His1076ArgfsTer6	frameshift_variant, stop_gained	Exon 10 of 10	1	NM_005357.4	ENSP00000244289.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 6 AN: 151792 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000218 AC: 29 AN: 1328322 Hom.: 0 Cov.: 30 AF XY: 0.0000291 AC XY: 19 AN XY: 652594

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: 0.000401

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.52e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000395 AC: 6 AN: 151900 Hom.: 0 Cov.: 30 AF XY: 0.0000539 AC XY: 4 AN XY: 74192

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;