17-43952807-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001394028.1(PYY):c.*149C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 803,240 control chromosomes in the GnomAD database, including 9,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1691 hom., cov: 32)
  • Exomes 𝑓: 0.092 (7760 hom.)
• Consequence: PYY NM_001394028.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.79

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-43952807-G-T is Benign according to our data. Variant chr17-43952807-G-T is described in ClinVar as [Benign]. Clinvar id is 1249578.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYY	NM_001394028.1	c.*149C>A		3_prime_UTR_variant	4/4	ENST00000692052.1
PYY	NM_001394029.1	c.*298C>A		3_prime_UTR_variant	3/3
PYY	NM_004160.6	c.*149C>A		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYY	ENST00000692052.1	c.*149C>A		3_prime_UTR_variant	4/4		NM_001394028.1	P1
PYY	ENST00000360085.6	c.*149C>A		3_prime_UTR_variant	7/7	1		P1
PYY	ENST00000592796.2	c.*298C>A		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15234 AN: 152134 Hom.: 1681 Cov.: 32

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0923 AC: 60116 AN: 650988 Hom.: 7760 Cov.: 9 AF XY: 0.0944 AC XY: 31595 AN XY: 334810

Gnomad4 AFR exome AF: 0.0857

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.0905

Gnomad4 EAS exome AF: 0.599

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.0452

Gnomad4 OTH exome AF: 0.0993

GnomAD4 genome AF: 0.100 AC: 15262 AN: 152252 Hom.: 1691 Cov.: 32 AF XY: 0.109 AC XY: 8144 AN XY: 74416

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.0901

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0474

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0322 Hom.: 22

Bravo AF: 0.106

Asia WGS AF: 0.362 AC: 1256 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

This variant is associated with the following publications: (PMID: 19820027) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.82
Dann	Benign	0.73

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: rs162431; hg19: chr17-42030175; COSMIC: COSV63970064; COSMIC: COSV63970064;