rs1012793001

Variant names:

• chr9-116154517-C-A
• rs1012793001
• NM_002581.5:c.345C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-116154517-C-A
• chr9-116154517-C-G
• chr9-116154517-C-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_002581.5(PAPPA):​c.345C>A​(p.Pro115Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,245,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P115P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: PAPPA NM_002581.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 0 publications found

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]

ENSG00000298241 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=1.17 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 27 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002581.5. 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
	PAPPA	NM_002581.5	MANE Select	c.345C>A	p.Pro115Pro	synonymous	Exon 1 of 22	NP_002572.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPPA	ENST00000328252.4	TSL:1 MANE Select	c.345C>A	p.Pro115Pro	synonymous	Exon 1 of 22	ENSP00000330658.3	Q13219
	ENSG00000298241	ENST00000754065.1		n.229+234G>T		intron	N/A
	ENSG00000298241	ENST00000754066.1		n.398+234G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000217 AC: 27 AN: 1245892 Hom.: 0 Cov.: 31 AF XY: 0.0000229 AC XY: 14 AN XY: 610620

African (AFR) AF: 0.00 AC: 0 AN: 25622

American (AMR) AF: 0.00 AC: 0 AN: 20956

Ashkenazi Jewish (ASJ) AF: 0.0000484 AC: 1 AN: 20650

East Asian (EAS) AF: 0.00 AC: 0 AN: 27510

South Asian (SAS) AF: 0.00 AC: 0 AN: 60770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3662

European-Non Finnish (NFE) AF: 0.0000258 AC: 26 AN: 1005936

Other (OTH) AF: 0.00 AC: 0 AN: 50506

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.96
PhyloP100		1.2

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: rs1012793001; hg19: chr9-118916796; COSMIC: COSV60284004;