Variant 17-43953334-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001394028.1(PYY):c.150C>T(p.Ala50Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,612,964 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 12 hom. )

Consequence

PYY
NM_001394028.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.748

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 17-43953334-G-A is Benign according to our data. Variant chr17-43953334-G-A is described in ClinVar as [Benign]. Clinvar id is 709316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.748 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00215 (3144/1460670) while in subpopulation MID AF= 0.0187 (108/5762). AF 95% confidence interval is 0.0159. There are 12 homozygotes in gnomad4_exome. There are 1567 alleles in male gnomad4_exome subpopulation. Median coverage is 49. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYY	NM_001394028.1 link	c.150C>T	p.Ala50Ala	synonymous_variant	2/4	ENST00000692052.1	NP_001380957.1
PYY	NM_004160.6 link	c.150C>T	p.Ala50Ala	synonymous_variant	5/7		NP_004151.4	P10082-1
PYY	NM_001394029.1 link	c.150C>T	p.Ala50Ala	synonymous_variant	2/3		NP_001380958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PYY	ENST00000692052.1 link	c.150C>T	p.Ala50Ala	synonymous_variant	2/4		NM_001394028.1	ENSP00000509262.1	P10082-1
PYY	ENST00000360085.6 link	c.150C>T	p.Ala50Ala	synonymous_variant	5/7	1		ENSP00000353198.1	P10082-1
PYY	ENST00000592796.2 link	c.150C>T	p.Ala50Ala	synonymous_variant	2/3	1		ENSP00000467310.1	P10082-2

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

322

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00238

AC:

586

AN:

246402

Hom.:

AF XY:

0.00236

AC XY:

316

AN XY:

134012

show subpopulations

Gnomad AFR exome

AF:

0.000957

Gnomad AMR exome

AF:

0.00170

Gnomad ASJ exome

AF:

0.0131

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.00122

Gnomad FIN exome

AF:

0.00252

Gnomad NFE exome

AF:

0.00239

Gnomad OTH exome

AF:

0.00451

GnomAD4 exome

AF:

0.00215

AC:

3144

AN:

1460670

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

1567

AN XY:

726664

show subpopulations

Gnomad4 AFR exome

AF:

0.00287

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.0148

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.00182

Gnomad4 OTH exome

AF:

0.00380

GnomAD4 genome

AF:

0.00211

AC:

322

AN:

152294

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.00398

Gnomad4 ASJ

AF:

0.0133

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00215

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00276

Hom.:

Bravo

AF:

0.00243

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00322

EpiControl

AF:

0.00321

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 18, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.96

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over