NM_001394028.1:c.109C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001394028.1(PYY):c.109C>G(p.Arg37Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,612,464 control chromosomes in the GnomAD database, including 806,224 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 76142 hom., cov: 33)

Exomes 𝑓: 1.0 ( 730082 hom. )

Consequence

PYY
NM_001394028.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.24

Publications

19 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.576002E-7).

BP6

Variant 17-43953375-G-C is Benign according to our data. Variant chr17-43953375-G-C is described in ClinVar as [Benign]. Clinvar id is 768890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.998 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYY	NM_001394028.1 link	c.109C>G	p.Arg37Gly	missense_variant	Exon 2 of 4	ENST00000692052.1	NP_001380957.1
PYY	NM_004160.6 link	c.109C>G	p.Arg37Gly	missense_variant	Exon 5 of 7		NP_004151.4	P10082-1
PYY	NM_001394029.1 link	c.109C>G	p.Arg37Gly	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.109C>G	p.Arg37Gly	missense_variant	Exon 2 of 4		NM_001394028.1	ENSP00000509262.1	P10082-1
PYY	ENST00000360085.6 link	c.109C>G	p.Arg37Gly	missense_variant	Exon 5 of 7	1		ENSP00000353198.1	P10082-1
PYY	ENST00000592796.2 link	c.109C>G	p.Arg37Gly	missense_variant	Exon 2 of 3	1		ENSP00000467310.1	P10082-2

Frequencies

GnomAD3 genomes

AF:

1.00

AC:

152167

AN:

152168

Hom.:

76083

Cov.:

show subpopulations

Gnomad AFR

AF:

1.00

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD2 exomes

AF:

1.00

AC:

244799

AN:

244802

AF XY:

1.00

show subpopulations

Gnomad AFR exome

AF:

1.00

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1460171

AN:

1460178

Hom.:

730082

Cov.:

AF XY:

1.00

AC XY:

726393

AN XY:

726396

show subpopulations

African (AFR)

AF:

1.00

AC:

33460

AN:

33460

American (AMR)

AF:

1.00

AC:

44521

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26088

AN:

26088

East Asian (EAS)

AF:

1.00

AC:

39660

AN:

39662

South Asian (SAS)

AF:

1.00

AC:

86090

AN:

86090

European-Finnish (FIN)

AF:

1.00

AC:

52946

AN:

52946

Middle Eastern (MID)

AF:

1.00

AC:

5760

AN:

5760

European-Non Finnish (NFE)

AF:

1.00

AC:

1111412

AN:

1111416

Other (OTH)

AF:

1.00

AC:

60234

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.632

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

1.00

AC:

152285

AN:

152286

Hom.:

76142

Cov.:

AF XY:

1.00

AC XY:

74441

AN XY:

74442

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

1.00

AC:

41578

AN:

41578

American (AMR)

AF:

1.00

AC:

15310

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5132

AN:

5132

South Asian (SAS)

AF:

1.00

AC:

4834

AN:

4834

European-Finnish (FIN)

AF:

1.00

AC:

10630

AN:

10630

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68007

AN:

68008

Other (OTH)

AF:

1.00

AC:

2116

AN:

2116

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

1.00

Hom.:

8451

Bravo

AF:

1.00

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3854

ExAC

AF:

1.00

AC:

120798

Asia WGS

AF:

1.00

AC:

3477

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 19, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.036

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.060

T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

6.6e-7

T;T

MetaSVM

Benign

-0.96

PhyloP100

2.2

PrimateAI

Uncertain

0.66

PROVEAN

Benign

6.3

N;.

REVEL

Benign

0.054

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.058

MPC

0.65

ClinPred

0.00094

GERP RS

2.4

Varity_R

0.068

gMVP

0.35

Mutation Taster

=77/23

polymorphism

(source)

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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NM_001394028.1:c.109C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over