17-43953298-CT-AG

Variant names:

• chr17-43953298-CT-AG
• NM_001394028.1:c.185_186delAGinsCT
• PYY p.Gln62Pro

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001394028.1(PYY):​c.185_186delAGinsCT​(p.Gln62Pro) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PYY NM_001394028.1 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45
• Publications: 0 publications found

Genes affected

PYY (HGNC:9748): (peptide YY) This gene encodes a member of the neuropeptide Y (NPY) family of peptides. The encoded preproprotein is proteolytically processed to generate two alternative peptide products that differ in length by three amino acids. These peptides, secreted by endocrine cells in the gut, exhibit different binding affinities for each of the neuropeptide Y receptors. Binding of the encoded peptides to these receptors mediates regulation of pancreatic secretion, gut mobility and energy homeostasis. Rare variations in this gene could increase susceptibility to obesity and elevated serum levels of the encoded peptides may be associated with anorexia nervosa. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394028.1. 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
	PYY	NM_001394028.1	MANE Select	c.185_186delAGinsCT	p.Gln62Pro	missense splice_region	N/A	NP_001380957.1	P10082-1
	PYY	NM_004160.6		c.185_186delAGinsCT	p.Gln62Pro	missense splice_region	N/A	NP_004151.4	P10082-1
	PYY	NM_001394029.1		c.185_186delAGinsCT	p.Gln62Pro	missense splice_region	N/A	NP_001380958.1	P10082-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYY	ENST00000692052.1	MANE Select	c.185_186delAGinsCT	p.Gln62Pro	missense splice_region	N/A	ENSP00000509262.1	P10082-1
	PYY	ENST00000360085.6	TSL:1	c.185_186delAGinsCT	p.Gln62Pro	missense splice_region	N/A	ENSP00000353198.1	P10082-1
	PYY	ENST00000592796.2	TSL:1	c.185_186delAGinsCT	p.Gln62Pro	missense splice_region	N/A	ENSP00000467310.1	P10082-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-42030666;