4-163351058-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006174.4(NPY5R):c.785C>A(p.Ser262Tyr) 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. 15/21 in silico tools predict a benign outcome for this variant. 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: 3.01

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3112019).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPY5R	NM_006174.4	c.785C>A	p.Ser262Tyr	missense_variant	4/4	ENST00000338566.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY5R	ENST00000338566.8	c.785C>A	p.Ser262Tyr	missense_variant	4/4	1	NM_006174.4	P1
NPY5R	ENST00000506953.1	c.785C>A	p.Ser262Tyr	missense_variant	1/1			P1
NPY5R	ENST00000515560.1	c.785C>A	p.Ser262Tyr	missense_variant	4/4	2		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

Oct 10, 2023

The c.785C>A (p.S262Y) alteration is located in exon 4 (coding exon 1) of the NPY5R gene. This alteration results from a C to A substitution at nucleotide position 785, causing the serine (S) at amino acid position 262 to be replaced by a tyrosine (Y). 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	0.097
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.14	T;T;T
Eigen	Benign	0.017
Eigen_PC	Benign	0.012
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.1	L;L;L
MutationTaster	Benign	0.78	D;D;D
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.14	T;T;T
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.78	P;P;P
Vest4		0.28
MutPred		0.43		Loss of disorder (P = 0.0127);Loss of disorder (P = 0.0127);Loss of disorder (P = 0.0127);
MVP		0.87
MPC		0.42
ClinPred		0.62	D
GERP RS		4.0
Varity_R		0.096
gMVP		0.27

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: chr4-164272210;