17-44001507-TCTC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000360085.6(PYY):c.-463+2881_-463+2883del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,008 control chromosomes in the GnomAD database, including 2,079 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2079 hom., cov: 28)
• Consequence: PYY ENST00000360085.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.39

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-44001507-TCTC-T is Benign according to our data. Variant chr17-44001507-TCTC-T is described in ClinVar as [Benign]. Clinvar id is 1221561.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYY	NM_004160.6	c.-463+2881_-463+2883del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYY	ENST00000360085.6	c.-463+2881_-463+2883del		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23291 AN: 151890 Hom.: 2078 Cov.: 28

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.153 AC: 23287 AN: 152008 Hom.: 2079 Cov.: 28 AF XY: 0.154 AC XY: 11423 AN XY: 74296

Gnomad4 AFR AF: 0.0779

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.128

Alfa AF: 0.184 Hom.: 349

Bravo AF: 0.138

Asia WGS AF: 0.0530 AC: 182 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs151305517; hg19: chr17-42078875;