10-46462271-C-T

Variant names:

• chr10-46462271-C-T
• rs782612038
• NM_005972.6:c.365G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_005972.6(NPY4R):​c.365G>A​(p.Cys122Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPY4R NM_005972.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54

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]

ENSG00000285402 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.93

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY4R	NM_005972.6	c.365G>A	p.Cys122Tyr	missense_variant	Exon 3 of 3	ENST00000374312.5	NP_005963.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY4R	ENST00000374312.5	c.365G>A	p.Cys122Tyr	missense_variant	Exon 3 of 3	1	NM_005972.6	ENSP00000363431.1
NPY4R	ENST00000612632.3	c.365G>A	p.Cys122Tyr	missense_variant	Exon 2 of 2	1		ENSP00000480883.1
ENSG00000285402	ENST00000616785.1	n.254-14207C>T		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.22e-7 AC: 1 AN: 1217038 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 614266

Gnomad4 AFR exome AF: 0.0000352

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.365G>A (p.C122Y) alteration is located in exon 3 (coding exon 1) of the NPY4R gene. This alteration results from a G to A substitution at nucleotide position 365, causing the cysteine (C) at amino acid position 122 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	Pathogenic	0.88
BayesDel_noAF	Pathogenic	0.19
CADD	Benign	23
DANN	Uncertain	0.99
MetaRNN	Pathogenic	0.93	D;D
PROVEAN	Pathogenic	-9.1	D;.
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.0040	D;D
Vest4		0.79
gMVP		0.98

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

Other links and lift over

dbSNP: rs782612038; hg19: chr10-47087148;