7-24285257-G-C

Position:

• chr7-24285257-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000905.4(NPY):​c.17G>C​(p.Arg6Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPY NM_000905.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.51

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]

LOC107986777 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPY	NM_000905.4	c.17G>C	p.Arg6Pro	missense_variant	2/4	ENST00000242152.7
LOC107986777	XR_001745132.2	n.209+34100C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY	ENST00000242152.7	c.17G>C	p.Arg6Pro	missense_variant	2/4	1	NM_000905.4	P1
NPY	ENST00000405982.1	c.17G>C	p.Arg6Pro	missense_variant	1/3	1		P1
NPY	ENST00000407573.5	c.17G>C	p.Arg6Pro	missense_variant	3/5	3		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2023

The c.17G>C (p.R6P) alteration is located in exon 2 (coding exon 1) of the NPY gene. This alteration results from a G to C substitution at nucleotide position 17, causing the arginine (R) at amino acid position 6 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	0.0048	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;T;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.70	.;.;T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.90	D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.17	B;B;B
Vest4		0.66
MutPred		0.49		Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);
MVP		0.56
MPC		1.9
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.35
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-24324876;