chr4-163326401-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000909.6(NPY1R):​c.154A>T​(p.Ile52Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

NPY1R
NM_000909.6 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1811659).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NPY1RNM_000909.6 linkuse as main transcriptc.154A>T p.Ile52Phe missense_variant 2/3 ENST00000296533.3
NPY1RXM_005263031.5 linkuse as main transcriptc.154A>T p.Ile52Phe missense_variant 2/3
NPY1RXM_011532010.4 linkuse as main transcriptc.154A>T p.Ile52Phe missense_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NPY1RENST00000296533.3 linkuse as main transcriptc.154A>T p.Ile52Phe missense_variant 2/31 NM_000909.6 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152170
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000384
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251136
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135722
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000198
AC:
29
AN:
1461796
Hom.:
0
Cov.:
31
AF XY:
0.0000193
AC XY:
14
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000731
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152170
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000384
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000330
AC:
4

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 submitterclinical testingAmbry GeneticsNov 09, 2023The c.154A>T (p.I52F) alteration is located in exon 2 (coding exon 1) of the NPY1R gene. This alteration results from a A to T substitution at nucleotide position 154, causing the isoleucine (I) at amino acid position 52 to be replaced by a phenylalanine (F). 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
0.12
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.21
T;.;.
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.83
T;D;D
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.7
N;D;D
REVEL
Benign
0.14
Sift
Benign
0.055
T;D;D
Sift4G
Benign
0.066
T;.;.
Polyphen
0.89
P;.;.
Vest4
0.50
MutPred
0.54
Loss of stability (P = 0.2112);Loss of stability (P = 0.2112);Loss of stability (P = 0.2112);
MVP
0.27
MPC
1.0
ClinPred
0.12
T
GERP RS
4.3
Varity_R
0.42
gMVP
0.65

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.

Other links and lift over

dbSNP: rs746038594; hg19: chr4-164247553; API