chr17-43952807-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394028.1(PYY):​c.*149C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 803,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: PYY NM_001394028.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYY	NM_001394028.1	c.*149C>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000692052.1	NP_001380957.1
PYY	NM_004160.6	c.*149C>G		3_prime_UTR_variant	Exon 7 of 7		NP_004151.4
PYY	NM_001394029.1	c.*298C>G		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>G		3_prime_UTR_variant	Exon 4 of 4		NM_001394028.1	ENSP00000509262.1
PYY	ENST00000360085.6	c.*149C>G		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000353198.1
PYY	ENST00000592796.2	c.*298C>G		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000467310.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000307 AC: 2 AN: 651332 Hom.: 0 Cov.: 9 AF XY: 0.00000299 AC XY: 1 AN XY: 334994

African (AFR) AF: 0.00 AC: 0 AN: 15214

American (AMR) AF: 0.000115 AC: 2 AN: 17358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14300

East Asian (EAS) AF: 0.00 AC: 0 AN: 30536

South Asian (SAS) AF: 0.00 AC: 0 AN: 46494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 453320

Other (OTH) AF: 0.00 AC: 0 AN: 32410

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74446

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

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 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.

Alfa AF: 0.00 Hom.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.80
DANN	Benign	0.57
PhyloP100		-1.8

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;