rs229969

Variant names:

• chr17-43953375-G-A
• rs229969
• NM_001394028.1:c.109C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-43953375-G-A
• chr17-43953375-G-C
• chr17-43953375-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394028.1(PYY):​c.109C>T​(p.Arg37Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R37G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PYY NM_001394028.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• Publications: 19 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20103714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYY	NM_001394028.1	c.109C>T	p.Arg37Cys	missense_variant	Exon 2 of 4	ENST00000692052.1	NP_001380957.1
PYY	NM_004160.6	c.109C>T	p.Arg37Cys	missense_variant	Exon 5 of 7		NP_004151.4
PYY	NM_001394029.1	c.109C>T	p.Arg37Cys	missense_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.109C>T	p.Arg37Cys	missense_variant	Exon 2 of 4		NM_001394028.1	ENSP00000509262.1
PYY	ENST00000360085.6	c.109C>T	p.Arg37Cys	missense_variant	Exon 5 of 7	1		ENSP00000353198.1
PYY	ENST00000592796.2	c.109C>T	p.Arg37Cys	missense_variant	Exon 2 of 3	1		ENSP00000467310.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460176 Hom.: 0 Cov.: 69 AF XY: 0.00 AC XY: 0 AN XY: 726394

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111416

Other (OTH) AF: 0.00 AC: 0 AN: 60234

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		2.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.027
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.24	B;.
Vest4		0.19
MutPred		0.60		Gain of catalytic residue at P36 (P = 0.0139);Gain of catalytic residue at P36 (P = 0.0139);
MVP		0.52
MPC		0.72
ClinPred		0.92	D
GERP RS		2.4
Varity_R		0.17
gMVP		0.44

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: rs229969; hg19: chr17-42030743;