17-43953963-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The ENST00000360085.6(PYY):c.-114G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 154,246 control chromosomes in the GnomAD database, including 28,981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (28523 hom., cov: 31)
  • Exomes 𝑓: 0.62 (458 hom.)
• Consequence: PYY ENST00000360085.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.307

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 17-43953963-C-T is Benign according to our data. Variant chr17-43953963-C-T is described in ClinVar as [Benign]. Clinvar id is 1301660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYY	NM_004160.6	c.-114G>A		5_prime_UTR_variant	4/7
PYY	NM_001394028.1			upstream_gene_variant		ENST00000692052.1
PYY	NM_001394029.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYY	ENST00000360085.6	c.-114G>A		5_prime_UTR_variant	4/7	1		P1
PYY	ENST00000692052.1			upstream_gene_variant			NM_001394028.1	P1
PYY	ENST00000592796.2			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91917 AN: 151836 Hom.: 28513 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.593

GnomAD4 exome AF: 0.619 AC: 1419 AN: 2292 Hom.: 458 Cov.: 0 AF XY: 0.624 AC XY: 741 AN XY: 1188

Gnomad4 AFR exome AF: 0.452

Gnomad4 AMR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.625

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.693

Gnomad4 NFE exome AF: 0.668

Gnomad4 OTH exome AF: 0.586

GnomAD4 genome AF: 0.605 AC: 91945 AN: 151954 Hom.: 28523 Cov.: 31 AF XY: 0.608 AC XY: 45179 AN XY: 74264

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.593

Alfa AF: 0.643 Hom.: 41508

Bravo AF: 0.587

Asia WGS AF: 0.532 AC: 1853 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital

Jan 02, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Benign	17
Dann	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2070592; hg19: chr17-42031331; COSMIC: COSV63970278; COSMIC: COSV63970278;