17-43952807-G-T

Variant names:

• chr17-43952807-G-T
• rs162431
• NM_001394028.1:c.*149C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001394028.1(PYY):​c.*149C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 803,240 control chromosomes in the GnomAD database, including 9,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1691 hom., cov: 32)
  • Exomes 𝑓: 0.092 (7760 hom.)
• Consequence: PYY NM_001394028.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.79
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-43952807-G-T is Benign according to our data. Variant chr17-43952807-G-T is described in ClinVar as [Benign]. Clinvar id is 1249578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYY	NM_001394028.1	c.*149C>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000692052.1	NP_001380957.1
PYY	NM_004160.6	c.*149C>A		3_prime_UTR_variant	Exon 7 of 7		NP_004151.4
PYY	NM_001394029.1	c.*298C>A		3_prime_UTR_variant	Exon 3 of 3		NP_001380958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYY	ENST00000692052.1	c.*149C>A		3_prime_UTR_variant	Exon 4 of 4		NM_001394028.1	ENSP00000509262.1
PYY	ENST00000360085.6	c.*149C>A		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000353198.1
PYY	ENST00000592796.2	c.*298C>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000467310.1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15234 AN: 152134 Hom.: 1681 Cov.: 32

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0923 AC: 60116 AN: 650988 Hom.: 7760 Cov.: 9 AF XY: 0.0944 AC XY: 31595 AN XY: 334810

African (AFR) AF: 0.0857 AC: 1303 AN: 15198

American (AMR) AF: 0.215 AC: 3716 AN: 17316

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 1293 AN: 14288

East Asian (EAS) AF: 0.599 AC: 18288 AN: 30526

South Asian (SAS) AF: 0.163 AC: 7550 AN: 46432

European-Finnish (FIN) AF: 0.105 AC: 3998 AN: 37946

Middle Eastern (MID) AF: 0.0754 AC: 282 AN: 3740

European-Non Finnish (NFE) AF: 0.0452 AC: 20468 AN: 453150

Other (OTH) AF: 0.0993 AC: 3218 AN: 32392

GnomAD4 genome AF: 0.100 AC: 15262 AN: 152252 Hom.: 1691 Cov.: 32 AF XY: 0.109 AC XY: 8144 AN XY: 74416

African (AFR) AF: 0.0871 AC: 3619 AN: 41558

American (AMR) AF: 0.180 AC: 2758 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 313 AN: 3472

East Asian (EAS) AF: 0.596 AC: 3070 AN: 5150

South Asian (SAS) AF: 0.181 AC: 873 AN: 4826

European-Finnish (FIN) AF: 0.109 AC: 1157 AN: 10618

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0474 AC: 3223 AN: 68010

Other (OTH) AF: 0.101 AC: 213 AN: 2116

Alfa AF: 0.0182 Hom.: 22

Bravo AF: 0.106

Asia WGS AF: 0.362 AC: 1256 AN: 3478

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 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 19820027) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.82
DANN	Benign	0.73
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs162431; hg19: chr17-42030175; COSMIC: COSV63970064; COSMIC: COSV63970064;