Variant 4-163326246-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000909.6(NPY1R):c.309G>C(p.Met103Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

NPY1R
NM_000909.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

Variant links:

Genes affected

NPY1R (HGNC:7956): (neuropeptide Y receptor Y1) This gene belongs to the G-protein-coupled receptor superfamily. The encoded transmembrane protein mediates the function of neuropeptide Y (NPY), a neurotransmitter, and peptide YY (PYY), a gastrointestinal hormone. The encoded receptor undergoes fast agonist-induced internalization through clathrin-coated pits and is subsequently recycled back to the cell membrane. Activation of Y1 receptors may result in mobilization of intracellular calcium and inhibition of adenylate cyclase activity. [provided by RefSeq, Aug 2013]

NPY1R links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NPY1R	NM_000909.6 linkuse as main transcript	c.309G>C	p.Met103Ile	missense_variant	2/3	ENST00000296533.3	NP_000900.1
NPY1R	XM_005263031.5 linkuse as main transcript	c.309G>C	p.Met103Ile	missense_variant	2/3		XP_005263088.1
NPY1R	XM_011532010.4 linkuse as main transcript	c.309G>C	p.Met103Ile	missense_variant	2/3		XP_011530312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NPY1R	ENST00000296533.3 linkuse as main transcript	c.309G>C	p.Met103Ile	missense_variant	2/3	1	NM_000909.6	ENSP00000354652	P1
NPY1R	ENST00000504391.5 linkuse as main transcript	c.-135G>C		5_prime_UTR_variant	3/5	5		ENSP00000422963
NPY1R	ENST00000509586.5 linkuse as main transcript	c.-106-315G>C		intron_variant		2		ENSP00000427284
NPY1R	ENST00000512819.1 linkuse as main transcript	c.-114-112G>C		intron_variant		4		ENSP00000421618

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2023

The c.309G>C (p.M103I) alteration is located in exon 2 (coding exon 1) of the NPY1R gene. This alteration results from a G to C substitution at nucleotide position 309, causing the methionine (M) at amino acid position 103 to be replaced by an isoleucine (I). 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

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.032

Polyphen

1.0

Vest4

0.75

MutPred

0.69

Gain of catalytic residue at M103 (P = 0.038);

MVP

0.76

MPC

1.7

ClinPred

0.99

GERP RS

5.8

Varity_R

0.90

gMVP

0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over