dbSNP rs752834121: PYY:p.Arg47Cys (chr17-43953345-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001394028.1(PYY):c.139C>T(p.Arg47Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,472 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R47S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PYY
NM_001394028.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.22

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYY	NM_001394028.1 link	c.139C>T	p.Arg47Cys	missense_variant	Exon 2 of 4	ENST00000692052.1	NP_001380957.1
PYY	NM_004160.6 link	c.139C>T	p.Arg47Cys	missense_variant	Exon 5 of 7		NP_004151.4	P10082-1
PYY	NM_001394029.1 link	c.139C>T	p.Arg47Cys	missense_variant	Exon 2 of 3		NP_001380958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PYY	ENST00000692052.1 link	c.139C>T	p.Arg47Cys	missense_variant	Exon 2 of 4		NM_001394028.1	ENSP00000509262.1	P10082-1
PYY	ENST00000360085.6 link	c.139C>T	p.Arg47Cys	missense_variant	Exon 5 of 7	1		ENSP00000353198.1	P10082-1
PYY	ENST00000592796.2 link	c.139C>T	p.Arg47Cys	missense_variant	Exon 2 of 3	1		ENSP00000467310.1	P10082-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

245292

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

6.85e-7

AC:

AN:

1460472

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726580

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.00

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111520

Other (OTH)

AF:

0.00

AC:

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

T;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.81

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Benign

-0.99

PhyloP100

2.2

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-6.2

D;.

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.89

P;.

Vest4

0.53

MutPred

0.51

Loss of disorder (P = 0.0204);Loss of disorder (P = 0.0204);

MVP

0.60

MPC

1.7

ClinPred

0.99

GERP RS

3.7

Varity_R

0.41

gMVP

0.42

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

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rs752834121

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over