rs162430

Positions:

• chr17-43953041-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001394029.1(PYY):​c.*64C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,590,194 control chromosomes in the GnomAD database, including 29,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (6392 hom., cov: 32)
  • Exomes 𝑓: 0.14 (23419 hom.)
• Consequence: PYY NM_001394029.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0700

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 17-43953041-G-A is Benign according to our data. Variant chr17-43953041-G-A is described in ClinVar as [Benign]. Clinvar id is 1243115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYY	NM_001394028.1	c.270-61C>T		intron_variant		ENST00000692052.1	NP_001380957.1
PYY	NM_001394029.1	c.*64C>T		3_prime_UTR_variant	3/3		NP_001380958.1
PYY	NM_004160.6	c.270-61C>T		intron_variant			NP_004151.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYY	ENST00000592796.2	c.*64C>T		3_prime_UTR_variant	3/3	1		ENSP00000467310.1
PYY	ENST00000692052.1	c.270-61C>T		intron_variant			NM_001394028.1	ENSP00000509262.1
PYY	ENST00000360085.6	c.270-61C>T		intron_variant		1		ENSP00000353198.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35699 AN: 152060 Hom.: 6348 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0954

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.135 AC: 194429 AN: 1438016 Hom.: 23419 Cov.: 31 AF XY: 0.137 AC XY: 97538 AN XY: 713794

Gnomad4 AFR exome AF: 0.456

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.680

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.0915

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.235 AC: 35804 AN: 152178 Hom.: 6392 Cov.: 32 AF XY: 0.240 AC XY: 17840 AN XY: 74394

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0954

Gnomad4 OTH AF: 0.220

Alfa AF: 0.134 Hom.: 1761

Bravo AF: 0.257

Asia WGS AF: 0.443 AC: 1538 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	This variant is associated with the following publications: (PMID: 14551916) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.8
DANN	Benign	0.92

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: rs162430; hg19: chr17-42030409; COSMIC: COSV63970071;