4-163350728-C-G

Position:

• chr4-163350728-C-G

Variant summary

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

The NM_006174.4(NPY5R):​c.455C>G​(p.Thr152Arg) 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: NPY5R NM_006174.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.80

Genes affected

NPY5R (HGNC:7958): (neuropeptide Y receptor Y5) The protein encoded by this gene is a receptor for neuropeptide Y and peptide YY. The encoded protein appears to be involved in regulating food intake, with defects in this gene being associated with eating disorders. Also, the encoded protein is involved in a pathway that protects neuroblastoma cells from chemotherapy-induced cell death, providing a possible therapeutic target against neuroblastoma. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Nov 2015]

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	Protein	UniProt
NPY5R	NM_006174.4	c.455C>G	p.Thr152Arg	missense_variant	4/4	ENST00000338566.8	NP_006165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY5R	ENST00000338566.8	c.455C>G	p.Thr152Arg	missense_variant	4/4	1	NM_006174.4	ENSP00000339377	P1
NPY5R	ENST00000506953.1	c.455C>G	p.Thr152Arg	missense_variant	1/1			ENSP00000423474	P1
NPY5R	ENST00000515560.1	c.455C>G	p.Thr152Arg	missense_variant	4/4	2		ENSP00000423917	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Nov 18, 2022

The c.455C>G (p.T152R) alteration is located in exon 4 (coding exon 1) of the NPY5R gene. This alteration results from a C to G substitution at nucleotide position 455, causing the threonine (T) at amino acid position 152 to be replaced by an arginine (R). 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	0.19
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	.;.;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.23
Sift	Benign	0.040	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.64	P;P;P
Vest4		0.63
MutPred		0.55		Gain of methylation at T152 (P = 0.0256);Gain of methylation at T152 (P = 0.0256);Gain of methylation at T152 (P = 0.0256);
MVP		0.69
MPC		0.84
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.54
gMVP		0.73

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-164271880;