Variant 17-43952978-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394028.1(PYY):c.272C>T(p.Ser91Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,414,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PYY
NM_001394028.1 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

Variant links:

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]

PYY links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12961489).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYY	NM_001394028.1 link	c.272C>T	p.Ser91Leu	missense_variant, splice_region_variant	4/4	ENST00000692052.1	NP_001380957.1
PYY	NM_004160.6 link	c.272C>T	p.Ser91Leu	missense_variant, splice_region_variant	7/7		NP_004151.4	P10082-1
PYY	NM_001394029.1 link	c.*127C>T		3_prime_UTR_variant	3/3		NP_001380958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PYY	ENST00000692052.1 link	c.272C>T	p.Ser91Leu	missense_variant, splice_region_variant	4/4		NM_001394028.1	ENSP00000509262.1	P10082-1
PYY	ENST00000360085.6 link	c.272C>T	p.Ser91Leu	missense_variant, splice_region_variant	7/7	1		ENSP00000353198.1	P10082-1
PYY	ENST00000592796.2 link	c.*127C>T		3_prime_UTR_variant	3/3	1		ENSP00000467310.1	P10082-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000465

AC:

AN:

215008

Hom.:

AF XY:

0.00

AC XY:

AN XY:

115212

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000354

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000106

AC:

AN:

1414464

Hom.:

Cov.:

AF XY:

0.00000859

AC XY:

AN XY:

698884

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000266

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000129

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.272C>T (p.S91L) alteration is located in exon 7 (coding exon 3) of the PYY gene. This alteration results from a C to T substitution at nucleotide position 272, causing the serine (S) at amino acid position 91 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.035

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.013

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.55

M_CAP

Benign

0.033

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

0.30

REVEL

Benign

0.070

Sift

Benign

0.53

Sift4G

Benign

0.56

Polyphen

0.98

Vest4

0.073

MutPred

0.14

Loss of phosphorylation at S91 (P = 0.0017);

MVP

0.54

MPC

0.50

ClinPred

0.21

GERP RS

4.5

Varity_R

0.086

gMVP

0.092

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over