10-116444457-G-A

Variant names:

• chr10-116444457-G-A
• rs200054779
• NM_001011709.3:c.400G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001011709.3(PNLIPRP3):​c.400G>A​(p.Val134Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. V134L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PNLIPRP3 NM_001011709.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37683144).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011709.3. 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
	PNLIPRP3	NM_001011709.3	MANE Select	c.400G>A	p.Val134Ile	missense	Exon 4 of 12	NP_001011709.2	Q17RR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNLIPRP3	ENST00000369230.4	TSL:1 MANE Select	c.400G>A	p.Val134Ile	missense	Exon 4 of 12	ENSP00000358232.3	Q17RR3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251404 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461102 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 726872

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111366

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.14
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.73	N
REVEL	Uncertain	0.29
Sift	Benign	0.081	T
Sift4G	Benign	0.16	T
Polyphen		0.95	P
Vest4		0.073
MutPred		0.75		Loss of methylation at R138 (P = 0.1265)
MVP		0.45
MPC		0.058
ClinPred		0.11	T
GERP RS		1.1
Varity_R		0.13
gMVP		0.64
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs200054779; hg19: chr10-118203969;