NM_006229.4:c.181A>G

Variant names:

• chr10-116591902-A-G
• rs11197744
• NM_006229.4:c.181A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006229.4(PNLIPRP1):​c.181A>G​(p.Asn61Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0257 in 1,614,070 control chromosomes in the GnomAD database, including 644 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 0.019 (53 hom., cov: 32)
  • Exomes 𝑓: 0.026 (591 hom.)
• Consequence: PNLIPRP1 NM_006229.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.20
• Publications: 12 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0066432655).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0195 (2967/152270) while in subpopulation NFE AF = 0.0274 (1861/68008). AF 95% confidence interval is 0.0263. There are 53 homozygotes in GnomAd4. There are 1463 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 53 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006229.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNLIPRP1	NM_006229.4	MANE Select	c.181A>G	p.Asn61Asp	missense	Exon 3 of 13	NP_006220.1
	PNLIPRP1	NM_001303135.1		c.181A>G	p.Asn61Asp	missense	Exon 3 of 13	NP_001290064.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNLIPRP1	ENST00000358834.9	TSL:1 MANE Select	c.181A>G	p.Asn61Asp	missense	Exon 3 of 13	ENSP00000351695.4
	PNLIPRP1	ENST00000525820.5	TSL:1	n.217A>G		non_coding_transcript_exon	Exon 3 of 12
	PNLIPRP1	ENST00000526223.5	TSL:1	n.217A>G		non_coding_transcript_exon	Exon 3 of 12

Frequencies

GnomAD3 genomes AF: 0.0195 AC: 2969 AN: 152152 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.00432

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0274

Gnomad OTH AF: 0.0182

GnomAD2 exomes AF: 0.0229 AC: 5739 AN: 251106 AF XY: 0.0244

Gnomad AFR exome AF: 0.00419

Gnomad AMR exome AF: 0.00836

Gnomad ASJ exome AF: 0.0100

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.0473

Gnomad NFE exome AF: 0.0281

Gnomad OTH exome AF: 0.0248

GnomAD4 exome AF: 0.0264 AC: 38580 AN: 1461800 Hom.: 591 Cov.: 31 AF XY: 0.0269 AC XY: 19537 AN XY: 727212

African (AFR) AF: 0.00350 AC: 117 AN: 33476

American (AMR) AF: 0.00924 AC: 413 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00953 AC: 249 AN: 26132

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39700

South Asian (SAS) AF: 0.0288 AC: 2485 AN: 86258

European-Finnish (FIN) AF: 0.0456 AC: 2433 AN: 53400

Middle Eastern (MID) AF: 0.0238 AC: 137 AN: 5768

European-Non Finnish (NFE) AF: 0.0283 AC: 31437 AN: 1111952

Other (OTH) AF: 0.0216 AC: 1302 AN: 60394

GnomAD4 genome AF: 0.0195 AC: 2967 AN: 152270 Hom.: 53 Cov.: 32 AF XY: 0.0196 AC XY: 1463 AN XY: 74464

African (AFR) AF: 0.00431 AC: 179 AN: 41562

American (AMR) AF: 0.0153 AC: 234 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0274 AC: 132 AN: 4824

European-Finnish (FIN) AF: 0.0445 AC: 472 AN: 10610

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0274 AC: 1861 AN: 68008

Other (OTH) AF: 0.0180 AC: 38 AN: 2114

Alfa AF: 0.0234 Hom.: 125

Bravo AF: 0.0160

TwinsUK AF: 0.0259 AC: 96

ALSPAC AF: 0.0330 AC: 127

ESP6500AA AF: 0.00409 AC: 18

ESP6500EA AF: 0.0283 AC: 243

ExAC AF: 0.0235 AC: 2857

Asia WGS AF: 0.00722 AC: 26 AN: 3478

EpiCase AF: 0.0275

EpiControl AF: 0.0256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0066	T
MetaSVM	Uncertain	0.59	D
MutationAssessor	Benign	1.9	L
PhyloP100		5.2
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.41
Sift	Benign	0.049	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.95	P
Vest4		0.13
MPC		0.18
ClinPred		0.034	T
GERP RS		5.7
Varity_R		0.49
gMVP		0.58
Mutation Taster		=94/6	polymorphism (auto)

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: rs11197744; hg19: chr10-118351414;