NM_001394028.1:c.209C>A

Variant summary

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

The NM_001394028.1(PYY):​c.209C>A​(p.Pro70Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,666 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. 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. P70R) 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

1
1
16

Clinical Significance

Not reported in ClinVar

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]

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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=0.12792829).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PYYNM_001394028.1 linkc.209C>A p.Pro70Gln missense_variant Exon 3 of 4 ENST00000692052.1 NP_001380957.1
PYYNM_004160.6 linkc.209C>A p.Pro70Gln missense_variant Exon 6 of 7 NP_004151.4 P10082-1
PYYNM_001394029.1 linkc.209C>A p.Pro70Gln missense_variant Exon 3 of 3 NP_001380958.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PYYENST00000692052.1 linkc.209C>A p.Pro70Gln missense_variant Exon 3 of 4 NM_001394028.1 ENSP00000509262.1 P10082-1
PYYENST00000360085.6 linkc.209C>A p.Pro70Gln missense_variant Exon 6 of 7 1 ENSP00000353198.1 P10082-1
PYYENST00000592796.2 linkc.209C>A p.Pro70Gln missense_variant Exon 3 of 3 1 ENSP00000467310.1 P10082-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461666
Hom.:
0
Cov.:
49
AF XY:
0.00
AC XY:
0
AN XY:
727150
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33474
American (AMR)
AF:
0.0000224
AC:
1
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26130
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53396
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111846
Other (OTH)
AF:
0.00
AC:
0
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.40
T;.
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.0
T
PhyloP100
1.2
PrimateAI
Benign
0.38
T
PROVEAN
Pathogenic
-5.0
D;.
REVEL
Benign
0.020
Sift
Benign
0.043
D;.
Sift4G
Benign
0.11
T;T
Polyphen
0.78
P;.
Vest4
0.25
MutPred
0.25
Gain of MoRF binding (P = 0.043);Gain of MoRF binding (P = 0.043);
MVP
0.25
MPC
1.0
ClinPred
0.52
D
GERP RS
2.8
Varity_R
0.12
gMVP
0.18

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

Other links and lift over

dbSNP: rs770520813; hg19: chr17-42030537; COSMIC: COSV63970898; API