17-43953299-T-G

Position:

• chr17-43953299-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001394028.1(PYY):​c.185A>C​(p.Gln62Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PYY NM_001394028.1 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.45

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYY	NM_001394028.1	c.185A>C	p.Gln62Pro	missense_variant	2/4	ENST00000692052.1	NP_001380957.1
PYY	NM_004160.6	c.185A>C	p.Gln62Pro	missense_variant	5/7		NP_004151.4
PYY	NM_001394029.1	c.185A>C	p.Gln62Pro	missense_variant	2/3		NP_001380958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYY	ENST00000692052.1	c.185A>C	p.Gln62Pro	missense_variant	2/4		NM_001394028.1	ENSP00000509262.1
PYY	ENST00000360085.6	c.185A>C	p.Gln62Pro	missense_variant	5/7	1		ENSP00000353198.1
PYY	ENST00000592796.2	c.185A>C	p.Gln62Pro	missense_variant	2/3	1		ENSP00000467310.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Obesity Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Feb 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.82	T
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.9	D;.
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;.
Sift4G	Benign	0.095	T;T
Polyphen		1.0	D;.
Vest4		0.58
MutPred		0.61		Gain of disorder (P = 0.0426);Gain of disorder (P = 0.0426);
MVP		0.58
MPC		1.6
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.89
gMVP		0.63

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: rs267606994; hg19: chr17-42030667;