10-116591825-G-T

Variant names:

• chr10-116591825-G-T
• rs782433696
• NM_006229.4:c.104G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006229.4(PNLIPRP1):​c.104G>T​(p.Gly35Val) 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 1,461,882 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PNLIPRP1 NM_006229.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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 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.104G>T	p.Gly35Val	missense_variant	Exon 3 of 13	ENST00000358834.9	NP_006220.1
PNLIPRP1	NM_001303135.1	c.104G>T	p.Gly35Val	missense_variant	Exon 3 of 13		NP_001290064.1
PNLIPRP1	XM_047425364.1	c.104G>T	p.Gly35Val	missense_variant	Exon 3 of 9		XP_047281320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIPRP1	ENST00000358834.9	c.104G>T	p.Gly35Val	missense_variant	Exon 3 of 13	1	NM_006229.4	ENSP00000351695.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251138 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135726

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	0.0073	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T;T;T;.;T;T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.085
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.63	T;.;T;T;T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.47	T;T;T;T;T;T;T
MetaSVM	Uncertain	0.67	D
MutationAssessor	Benign	1.6	.;L;L;.;.;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D;D;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.029	D;D;D;T;D;D;D
Sift4G	Benign	0.38	T;D;D;T;T;D;D
Polyphen		0.68	.;P;P;.;.;.;.
Vest4		0.33, 0.33, 0.33
MutPred		0.68		Loss of disorder (P = 0.1148);Loss of disorder (P = 0.1148);Loss of disorder (P = 0.1148);Loss of disorder (P = 0.1148);Loss of disorder (P = 0.1148);Loss of disorder (P = 0.1148);Loss of disorder (P = 0.1148);
MVP		0.95
MPC		0.15
ClinPred		0.83	D
GERP RS		2.4
Varity_R		0.46
gMVP		0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs782433696; hg19: chr10-118351337;