17-43953137-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394028.1(PYY):c.241G>A(p.Asp81Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PYY
NM_001394028.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18188801).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYY	NM_001394028.1 link	c.241G>A	p.Asp81Asn	missense_variant	Exon 3 of 4	ENST00000692052.1	NP_001380957.1
PYY	NM_004160.6 link	c.241G>A	p.Asp81Asn	missense_variant	Exon 6 of 7		NP_004151.4	P10082-1
PYY	NM_001394029.1 link	c.241G>A	p.Asp81Asn	missense_variant	Exon 3 of 3		NP_001380958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PYY	ENST00000692052.1 link	c.241G>A	p.Asp81Asn	missense_variant	Exon 3 of 4		NM_001394028.1	ENSP00000509262.1	P10082-1
PYY	ENST00000360085.6 link	c.241G>A	p.Asp81Asn	missense_variant	Exon 6 of 7	1		ENSP00000353198.1	P10082-1
PYY	ENST00000592796.2 link	c.241G>A	p.Asp81Asn	missense_variant	Exon 3 of 3	1		ENSP00000467310.1	P10082-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000798

AC:

AN:

250734

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

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:

0.00000205

AC:

AN:

1461720

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727170

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.0000671

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111908

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.241G>A (p.D81N) alteration is located in exon 6 (coding exon 2) of the PYY gene. This alteration results from a G to A substitution at nucleotide position 241, causing the aspartic acid (D) at amino acid position 81 to be replaced by an asparagine (N). 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

0.095

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

0.0050

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.1

PhyloP100

1.2

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.6

D;.

REVEL

Benign

0.072

Sift

Benign

0.10

T;.

Sift4G

Benign

0.23

T;T

Polyphen

1.0

D;.

Vest4

0.29

MutPred

0.14

Loss of disorder (P = 0.1132);Loss of disorder (P = 0.1132);

MVP

0.51

MPC

0.81

ClinPred

0.51

GERP RS

3.5

Varity_R

0.15

gMVP

0.23

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over