Genetic Variant NM_001394028.1:c.272C>T (chr17-43952978-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/21 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

Publications

3 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=0.12961489).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394028.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PYY	NM_001394028.1	MANE Select	c.272C>T	p.Ser91Leu	missense splice_region	Exon 4 of 4	NP_001380957.1	P10082-1
PYY	NM_004160.6		c.272C>T	p.Ser91Leu	missense splice_region	Exon 7 of 7	NP_004151.4	P10082-1
PYY	NM_001394029.1		c.*127C>T		3_prime_UTR	Exon 3 of 3	NP_001380958.1	P10082-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PYY	ENST00000692052.1	MANE Select	c.272C>T	p.Ser91Leu	missense splice_region	Exon 4 of 4	ENSP00000509262.1	P10082-1
PYY	ENST00000360085.6	TSL:1	c.272C>T	p.Ser91Leu	missense splice_region	Exon 7 of 7	ENSP00000353198.1	P10082-1
PYY	ENST00000592796.2	TSL:1	c.*127C>T		3_prime_UTR	Exon 3 of 3	ENSP00000467310.1	P10082-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000465

AC:

AN:

215008

AF XY:

0.00

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 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

African (AFR)

AF:

0.00

AC:

AN:

31734

American (AMR)

AF:

0.0000266

AC:

AN:

37616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23158

East Asian (EAS)

AF:

0.00

AC:

AN:

39232

South Asian (SAS)

AF:

0.00

AC:

AN:

79368

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5520

European-Non Finnish (NFE)

AF:

0.0000129

AC:

AN:

1087788

Other (OTH)

AF:

0.00

AC:

AN:

58126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

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

PhyloP100

1.6

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

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over