chr10-116596218-A-G

Position:

• chr10-116596218-A-G

Variant summary

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

The NM_006229.4(PNLIPRP1):​c.470A>G​(p.Glu157Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 6.9e-7 (0 hom.)
• Consequence: PNLIPRP1 NM_006229.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.615

Genes affected

PNLIPRP1 (HGNC:9156): (pancreatic lipase related protein 1) Predicted to enable calcium ion binding activity. Predicted to be involved in lipid catabolic process. Predicted to be located in extracellular region. Biomarker of prostate cancer. [provided by Alliance of Genome Resources, Apr 2022]

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=0.3315146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNLIPRP1	NM_006229.4	c.470A>G	p.Glu157Gly	missense_variant	6/13	ENST00000358834.9
PNLIPRP1	NM_001303135.1	c.470A>G	p.Glu157Gly	missense_variant	6/13
PNLIPRP1	XM_047425364.1	c.470A>G	p.Glu157Gly	missense_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNLIPRP1	ENST00000358834.9	c.470A>G	p.Glu157Gly	missense_variant	6/13	1	NM_006229.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453046 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723432

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: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.470A>G (p.E157G) alteration is located in exon 6 (coding exon 5) of the PNLIPRP1 gene. This alteration results from a A to G substitution at nucleotide position 470, causing the glutamic acid (E) at amino acid position 157 to be replaced by a glycine (G). 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	0.089
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Uncertain	0.63	D;D;D;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.11	T;.;T;T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Uncertain	-0.045	T
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.9	D;D;D;N
REVEL	Uncertain	0.35
Sift	Benign	0.27	T;T;T;T
Sift4G	Benign	0.37	T;T;T;T
Polyphen		0.0020	.;B;B;.
Vest4		0.14
MutPred		0.54		Loss of stability (P = 0.0543);Loss of stability (P = 0.0543);Loss of stability (P = 0.0543);.;
MVP		0.95
MPC		0.045
ClinPred		0.12	T
GERP RS		5.4
Varity_R		0.21
gMVP		0.32

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: chr10-118355730;