rs5571

Variant names:

• chr7-24285304-C-A
• rs5571
• NM_000905.4:c.64C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-24285304-C-A
• chr7-24285304-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000905.4(NPY):​c.64C>A​(p.Leu22Met) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPY NM_000905.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.666
• Publications: 6 publications found

Genes affected

NPY (HGNC:7955): (neuropeptide Y) This gene encodes a neuropeptide that is widely expressed in the central nervous system and influences many physiological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. The neuropeptide functions through G protein-coupled receptors to inhibit adenylyl cyclase, activate mitogen-activated protein kinase (MAPK), regulate intracellular calcium levels, and activate potassium channels. A polymorphism in this gene resulting in a change of leucine 7 to proline in the signal peptide is associated with elevated cholesterol levels, higher alcohol consumption, and may be a risk factor for various metabolic and cardiovascular diseases. The protein also exhibits antimicrobial activity against bacteria and fungi. [provided by RefSeq, Oct 2014]

ENSG00000228944 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38417208).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000905.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	NM_000905.4	MANE Select	c.64C>A	p.Leu22Met	missense	Exon 2 of 4	NP_000896.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY	ENST00000242152.7	TSL:1 MANE Select	c.64C>A	p.Leu22Met	missense	Exon 2 of 4	ENSP00000242152.2
	NPY	ENST00000405982.1	TSL:1	c.64C>A	p.Leu22Met	missense	Exon 1 of 3	ENSP00000385282.1
	NPY	ENST00000407573.5	TSL:3	c.64C>A	p.Leu22Met	missense	Exon 3 of 5	ENSP00000384364.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.67
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.16
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.10		Gain of helix (P = 0.132)
MVP		0.16
MPC		1.6
ClinPred		0.99	D
GERP RS		3.6
PromoterAI		-0.014	Neutral
Varity_R		0.37
gMVP		0.55
Mutation Taster		=89/11	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: rs5571; hg19: chr7-24324923;