10-46462341-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_005972.6(NPY4R):​c.295G>T​(p.Ala99Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.25 ( 15 hom., cov: 25)
Exomes 𝑓: 0.25 ( 21 hom. )
Failed GnomAD Quality Control

Consequence

NPY4R
NM_005972.6 missense

Scores

3
4

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.822
Variant links:
Genes affected
NPY4R (HGNC:9329): (neuropeptide Y receptor Y4) Enables pancreatic polypeptide receptor activity and peptide hormone binding activity. Involved in G protein-coupled receptor signaling pathway. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.22038004).
BP6
Variant 10-46462341-C-A is Benign according to our data. Variant chr10-46462341-C-A is described in ClinVar as [Benign]. Clinvar id is 768356.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NPY4RNM_005972.6 linkuse as main transcriptc.295G>T p.Ala99Ser missense_variant 3/3 ENST00000374312.5 NP_005963.4 P50391

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NPY4RENST00000374312.5 linkuse as main transcriptc.295G>T p.Ala99Ser missense_variant 3/31 NM_005972.6 ENSP00000363431.1 P50391
NPY4RENST00000612632.3 linkuse as main transcriptc.295G>T p.Ala99Ser missense_variant 2/21 ENSP00000480883.1 P50391
ENSG00000285402ENST00000616785.1 linkuse as main transcriptn.254-14137C>A intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
32130
AN:
129680
Hom.:
15
Cov.:
25
FAILED QC
Gnomad AFR
AF:
0.251
Gnomad AMI
AF:
0.227
Gnomad AMR
AF:
0.298
Gnomad ASJ
AF:
0.266
Gnomad EAS
AF:
0.197
Gnomad SAS
AF:
0.351
Gnomad FIN
AF:
0.223
Gnomad MID
AF:
0.269
Gnomad NFE
AF:
0.235
Gnomad OTH
AF:
0.233
GnomAD4 exome
Data not reliable, filtered out with message: InbreedingCoeff
AF:
0.245
AC:
296225
AN:
1207646
Hom.:
21
Cov.:
28
AF XY:
0.248
AC XY:
149367
AN XY:
602138
show subpopulations
Gnomad4 AFR exome
AF:
0.251
Gnomad4 AMR exome
AF:
0.333
Gnomad4 ASJ exome
AF:
0.265
Gnomad4 EAS exome
AF:
0.212
Gnomad4 SAS exome
AF:
0.348
Gnomad4 FIN exome
AF:
0.238
Gnomad4 NFE exome
AF:
0.234
Gnomad4 OTH exome
AF:
0.252
GnomAD4 genome
Data not reliable, filtered out with message: InbreedingCoeff
AF:
0.248
AC:
32162
AN:
129782
Hom.:
15
Cov.:
25
AF XY:
0.250
AC XY:
15837
AN XY:
63382
show subpopulations
Gnomad4 AFR
AF:
0.251
Gnomad4 AMR
AF:
0.299
Gnomad4 ASJ
AF:
0.266
Gnomad4 EAS
AF:
0.197
Gnomad4 SAS
AF:
0.352
Gnomad4 FIN
AF:
0.223
Gnomad4 NFE
AF:
0.235
Gnomad4 OTH
AF:
0.236

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_noAF
Benign
-0.38
CADD
Benign
18
DANN
Uncertain
0.99
MetaRNN
Benign
0.22
T;T
PROVEAN
Benign
-1.4
N;.
Sift
Uncertain
0.0060
D;.
Sift4G
Uncertain
0.013
D;D
Vest4
0.26
gMVP
0.90

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

LitVar

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

Other links and lift over

dbSNP: rs1197874424; hg19: chr10-47087078; COSMIC: COSV65398480; API