10-46462270-GC-AA

Variant names:

• chr10-46462270-GC-AA
• NM_005972.6:c.365_366delGCinsTT
• NPY4R p.Cys122Phe

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_005972.6(NPY4R):​c.365_366delGCinsTT​(p.Cys122Phe) variant causes a missense change involving the alteration of a conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C122Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 19)
• Consequence: NPY4R NM_005972.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.54
• Publications: 0 publications found

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:):

LINC00842 (HGNC:44989): (long intergenic non-protein coding RNA 842)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005972.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY4R	NM_005972.6	MANE Select	c.365_366delGCinsTT	p.Cys122Phe	missense	N/A	NP_005963.4
	NPY4R	NM_001278794.2		c.365_366delGCinsTT	p.Cys122Phe	missense	N/A	NP_001265723.1	P50391

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY4R	ENST00000374312.5	TSL:1 MANE Select	c.365_366delGCinsTT	p.Cys122Phe	missense	N/A	ENSP00000363431.1	P50391
	NPY4R	ENST00000612632.3	TSL:1	c.365_366delGCinsTT	p.Cys122Phe	missense	N/A	ENSP00000480883.1	P50391
	NPY4R	ENST00000908575.1		c.365_366delGCinsTT	p.Cys122Phe	missense	N/A	ENSP00000578634.1

Frequencies

GnomAD3 genomes Cov.: 19

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-47087149;