10-116638383-A-T

Variant names:

• chr10-116638383-A-T
• rs4751996
• ENST00000579578.6:c.1081A>T
• PNLIPRP2 p.Ile361Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000579578.6(PNLIPRP2):​c.1081A>T​(p.Ile361Leu) 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. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I361V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PNLIPRP2 ENST00000579578.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 17 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16487807).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000579578.6. 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
	PNLIPRP2	NR_103727.2		n.1107A>T		non_coding_transcript_exon	Exon 11 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNLIPRP2	ENST00000579578.6	TSL:2	c.1081A>T	p.Ile361Leu	missense	Exon 11 of 13	ENSP00000463502.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1125988 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 568232

African (AFR) AF: 0.00 AC: 0 AN: 26490

American (AMR) AF: 0.00 AC: 0 AN: 35316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23262

East Asian (EAS) AF: 0.00 AC: 0 AN: 36408

South Asian (SAS) AF: 0.00 AC: 0 AN: 73530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5198

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 826688

Other (OTH) AF: 0.00 AC: 0 AN: 49074

GnomAD4 genome Cov.: 31

Alfa AF: 0.00000681 Hom.: 21097

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Benign	0.87
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.66	T
PhyloP100		1.5
PrimateAI	Benign	0.37	T
Varity_R		0.067

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4751996;

hg19: chr10-118397894;