9-116327693-G-C

Position:

• chr9-116327693-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002581.5(PAPPA):​c.3148-3551G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,060 control chromosomes in the GnomAD database, including 30,926 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 0.62 (30926 hom., cov: 31)
• Consequence: PAPPA NM_002581.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.925

Genes affected

PAPPA (HGNC:8602): (pappalysin 1) This gene encodes a secreted metalloproteinase which cleaves insulin-like growth factor binding proteins (IGFBPs). Following IGFBP cleavage, insulin growth factors dissociate from IGFBPs and bind to IGF receptors, resulting in activation of the IGF pathway. The encoded protein plays a role in bone formation, inflammation, wound healing and female fertility. Enhanced expression of this protein is associated with diabetic nephropathy in human patients and this protein may promote tumor invasion and growth in various human cancers. [provided by RefSeq, Aug 2017]

PAPPA-AS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPPA	NM_002581.5	c.3148-3551G>C		intron_variant		ENST00000328252.4	NP_002572.2
PAPPA	XM_017014784.3	c.3148-4640G>C		intron_variant			XP_016870273.1
PAPPA	XM_006717129.4	c.1054-3551G>C		intron_variant			XP_006717192.1
PAPPA-AS2	NR_170222.1	n.81-7893C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPPA	ENST00000328252.4	c.3148-3551G>C		intron_variant		1	NM_002581.5	ENSP00000330658.3

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94913 AN: 151942 Hom.: 30926 Cov.: 31

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.645

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.624 AC: 94938 AN: 152060 Hom.: 30926 Cov.: 31 AF XY: 0.633 AC XY: 47038 AN XY: 74342

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.649

Alfa AF: 0.532 Hom.: 1585

Bravo AF: 0.609

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs10513273; hg19: chr9-119089972; COSMIC: COSV60279836; COSMIC: COSV60279836;