10-116596274-G-T

Variant names:

• chr10-116596274-G-T
• rs782722033
• NM_006229.4:c.526G>T

Variant summary

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

The NM_006229.4(PNLIPRP1):​c.526G>T​(p.Val176Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V176M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PNLIPRP1 NM_006229.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNLIPRP1	NM_006229.4	c.526G>T	p.Val176Leu	missense_variant	Exon 6 of 13	ENST00000358834.9	NP_006220.1
PNLIPRP1	NM_001303135.1	c.526G>T	p.Val176Leu	missense_variant	Exon 6 of 13		NP_001290064.1
PNLIPRP1	XM_047425364.1	c.526G>T	p.Val176Leu	missense_variant	Exon 6 of 9		XP_047281320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIPRP1	ENST00000358834.9	c.526G>T	p.Val176Leu	missense_variant	Exon 6 of 13	1	NM_006229.4	ENSP00000351695.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461768 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727192

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111898

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T;T;T;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	0.0082
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.57	T;.;T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.67	D;D;D;D;D
MetaSVM	Uncertain	0.051	D
MutationAssessor	Benign	1.6	.;L;L;.;.
PhyloP100		3.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N;N;N;N;N
REVEL	Uncertain	0.43
Sift	Benign	0.36	T;T;T;T;T
Sift4G	Benign	0.30	T;T;T;T;T
Polyphen		0.0080	.;B;B;.;.
Vest4		0.45, 0.45
MutPred		0.80		Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;Gain of helix (P = 0.132);
MVP		0.89
MPC		0.041
ClinPred		0.31	T
GERP RS		5.1
Varity_R		0.38
gMVP		0.74
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs782722033; hg19: chr10-118355786;