10-116455782-C-T

Variant names:

• chr10-116455782-C-T
• rs144686516
• NM_001011709.3:c.517C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001011709.3(PNLIPRP3):​c.517C>T​(p.Leu173Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,613,722 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00034 (1 hom.)
• Consequence: PNLIPRP3 NM_001011709.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.874

Genes affected

PNLIPRP3 (HGNC:23492): (pancreatic lipase related protein 3) Predicted to enable triglyceride lipase activity. Predicted to be involved in lipid catabolic process. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=0.874 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNLIPRP3	NM_001011709.3	c.517C>T	p.Leu173Leu	synonymous_variant	Exon 5 of 12	ENST00000369230.4	NP_001011709.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNLIPRP3	ENST00000369230.4	c.517C>T	p.Leu173Leu	synonymous_variant	Exon 5 of 12	1	NM_001011709.3	ENSP00000358232.3

Frequencies

GnomAD3 genomes AF: 0.000244 AC: 37 AN: 151748 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000953

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000472

Gnomad OTH AF: 0.000481

GnomAD3 exomes AF: 0.000255 AC: 64 AN: 251286 Hom.: 0 AF XY: 0.000272 AC XY: 37 AN XY: 135832

Gnomad AFR exome AF: 0.0000615

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: 0.000185

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000344 AC: 503 AN: 1461856 Hom.: 1 Cov.: 31 AF XY: 0.000362 AC XY: 263 AN XY: 727224

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.000433

Gnomad4 OTH exome AF: 0.000149

GnomAD4 genome AF: 0.000244 AC: 37 AN: 151866 Hom.: 0 Cov.: 33 AF XY: 0.000229 AC XY: 17 AN XY: 74224

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000953

Gnomad4 NFE AF: 0.000472

Gnomad4 OTH AF: 0.000476

Alfa AF: 0.000294 Hom.: 0

Bravo AF: 0.000291

EpiCase AF: 0.000383

EpiControl AF: 0.000653

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.9
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs144686516; hg19: chr10-118215294; COSMIC: COSV100982557;