Variant chr17-43953299-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001394028.1(PYY):c.185A>G(p.Gln62Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PYY
NM_001394028.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.45

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYY	NM_001394028.1 linkuse as main transcript	c.185A>G	p.Gln62Arg	missense_variant	2/4	ENST00000692052.1	NP_001380957.1
PYY	NM_004160.6 linkuse as main transcript	c.185A>G	p.Gln62Arg	missense_variant	5/7		NP_004151.4	P10082-1
PYY	NM_001394029.1 linkuse as main transcript	c.185A>G	p.Gln62Arg	missense_variant	2/3		NP_001380958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PYY	ENST00000692052.1 linkuse as main transcript	c.185A>G	p.Gln62Arg	missense_variant	2/4		NM_001394028.1	ENSP00000509262.1	P10082-1
PYY	ENST00000360085.6 linkuse as main transcript	c.185A>G	p.Gln62Arg	missense_variant	5/7	1		ENSP00000353198.1	P10082-1
PYY	ENST00000592796.2 linkuse as main transcript	c.185A>G	p.Gln62Arg	missense_variant	2/3	1		ENSP00000467310.1	P10082-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000818

AC:

AN:

244558

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

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:

0.00000137

AC:

AN:

1459920

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.71

T;T

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Benign

-0.48

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-4.0

D;.

REVEL

Uncertain

0.50

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.022

D;D

Polyphen

1.0

D;.

Vest4

0.71

MutPred

0.75

Gain of MoRF binding (P = 0.0432);Gain of MoRF binding (P = 0.0432);

MVP

0.68

MPC

0.69

ClinPred

0.95

GERP RS

4.6

Varity_R

0.80

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over