10-116631255-A-G

Variant names:

• chr10-116631255-A-G
• ENST00000579578.6:c.715A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000579578.6(PNLIPRP2):​c.715A>G​(p.Lys239Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PNLIPRP2 ENST00000579578.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15

Genes affected

PNLIPRP2 (HGNC:9157): (pancreatic lipase related protein 2 (gene/pseudogene)) This gene encodes a lipase that hydrolyzes galactolipids, the main components of plant membrane lipids. An allelic polymorphism in this gene results in both coding and non-coding variants; the reference genome represents the non-coding allele. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35624874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNLIPRP2	NR_103727.2	n.741A>G		non_coding_transcript_exon_variant	Exon 8 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIPRP2	ENST00000579578.6	c.715A>G	p.Lys239Glu	missense_variant	Exon 8 of 13	2		ENSP00000463502.4
PNLIPRP2	ENST00000588823.1	n.313A>G		non_coding_transcript_exon_variant	Exon 4 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1420652 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 702336

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.718A>G (p.K240E) alteration is located in exon 8 (coding exon 8) of the PNLIPRP2 gene. This alteration results from a A to G substitution at nucleotide position 718, causing the lysine (K) at amino acid position 240 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.017	T;T
Eigen	Benign	-0.014
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.13	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.39	T
PrimateAI	Benign	0.45	T
Polyphen		0.0050	.;B
Vest4		0.46
MutPred		0.66		Loss of ubiquitination at K239 (P = 0.0183);Loss of ubiquitination at K239 (P = 0.0183);
MVP		0.83
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.20

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-118390766;