Genetic Variant NPY5R:p.Ala14Ser (chr4-163350313-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006174.4(NPY5R):c.40G>T(p.Ala14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. A14P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NPY5R
NM_006174.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.674

Publications

0 publications found

Variant links:

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]

NPY5R links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0668011).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006174.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPY5R	NM_006174.4	MANE Select	c.40G>T	p.Ala14Ser	missense	Exon 4 of 4	NP_006165.1	Q15761
NPY5R	NM_001317091.2		c.40G>T	p.Ala14Ser	missense	Exon 4 of 4	NP_001304020.1	Q15761
NPY5R	NM_001317092.2		c.40G>T	p.Ala14Ser	missense	Exon 5 of 5	NP_001304021.1	Q15761

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPY5R	ENST00000338566.8	TSL:1 MANE Select	c.40G>T	p.Ala14Ser	missense	Exon 4 of 4	ENSP00000339377.3	Q15761
NPY5R	ENST00000506953.1	TSL:6	c.40G>T	p.Ala14Ser	missense	Exon 1 of 1	ENSP00000423474.1	Q15761
NPY5R	ENST00000515560.1	TSL:2	c.40G>T	p.Ala14Ser	missense	Exon 4 of 4	ENSP00000423917.1	Q15761

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1442986

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32700

American (AMR)

AF:

0.00

AC:

AN:

42666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25454

East Asian (EAS)

AF:

0.00

AC:

AN:

39304

South Asian (SAS)

AF:

0.00

AC:

AN:

84942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1099694

Other (OTH)

AF:

0.00

AC:

AN:

59402

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.3

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.068

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.40

M_CAP

Benign

0.017

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.67

PrimateAI

Benign

0.26

PROVEAN

Benign

0.010

REVEL

Benign

0.027

Sift

Benign

0.41

Sift4G

Benign

0.27

Polyphen

0.0010

Vest4

0.075

MutPred

0.35

Gain of disorder (P = 0.0332)

MVP

0.61

MPC

0.18

ClinPred

0.10

GERP RS

2.6

PromoterAI

-0.017

Neutral

(source)

Varity_R

0.030

gMVP

0.14

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over