17-43953334-G-A

Variant names:

• chr17-43953334-G-A
• rs138375613
• NM_001394028.1:c.150C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.748
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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. GnomAdExome4 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 GnomAdExome4. There are 1567 alleles in the male GnomAdExome4 subpopulation. Median coverage is 49. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYY	NM_001394028.1	c.150C>T	p.Ala50Ala	synonymous_variant	Exon 2 of 4	ENST00000692052.1	NP_001380957.1
PYY	NM_004160.6	c.150C>T	p.Ala50Ala	synonymous_variant	Exon 5 of 7		NP_004151.4
PYY	NM_001394029.1	c.150C>T	p.Ala50Ala	synonymous_variant	Exon 2 of 3		NP_001380958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYY	ENST00000692052.1	c.150C>T	p.Ala50Ala	synonymous_variant	Exon 2 of 4		NM_001394028.1	ENSP00000509262.1
PYY	ENST00000360085.6	c.150C>T	p.Ala50Ala	synonymous_variant	Exon 5 of 7	1		ENSP00000353198.1
PYY	ENST00000592796.2	c.150C>T	p.Ala50Ala	synonymous_variant	Exon 2 of 3	1		ENSP00000467310.1

Frequencies

GnomAD3 genomes AF: 0.00212 AC: 322 AN: 152176 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.00238 AC: 586 AN: 246402 AF XY: 0.00236

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 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.: 12 Cov.: 49 AF XY: 0.00216 AC XY: 1567 AN XY: 726664

African (AFR) AF: 0.00287 AC: 96 AN: 33460

American (AMR) AF: 0.00215 AC: 96 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.0148 AC: 385 AN: 26094

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39662

South Asian (SAS) AF: 0.00107 AC: 92 AN: 86150

European-Finnish (FIN) AF: 0.00217 AC: 115 AN: 53102

Middle Eastern (MID) AF: 0.0187 AC: 108 AN: 5762

European-Non Finnish (NFE) AF: 0.00182 AC: 2022 AN: 1111586

Other (OTH) AF: 0.00380 AC: 229 AN: 60292

GnomAD4 genome AF: 0.00211 AC: 322 AN: 152294 Hom.: 0 Cov.: 33 AF XY: 0.00203 AC XY: 151 AN XY: 74462

African (AFR) AF: 0.000673 AC: 28 AN: 41584

American (AMR) AF: 0.00398 AC: 61 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4832

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10626

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00215 AC: 146 AN: 68012

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00276 Hom.: 0

Bravo AF: 0.00243

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00322

EpiControl AF: 0.00321

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 18, 2018

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
BayesDel_noAF	Benign	-0.48
CADD	Benign	10
DANN	Benign	0.96
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs138375613; hg19: chr17-42030702;