NM_005972.6:c.365G>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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 2 ACMG points.

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

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.365G>A	p.Cys122Tyr	missense	Exon 3 of 3	NP_005963.4
	NPY4R	NM_001278794.2		c.365G>A	p.Cys122Tyr	missense	Exon 2 of 2	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.365G>A	p.Cys122Tyr	missense	Exon 3 of 3	ENSP00000363431.1	P50391
	NPY4R	ENST00000612632.3	TSL:1	c.365G>A	p.Cys122Tyr	missense	Exon 2 of 2	ENSP00000480883.1	P50391
	NPY4R	ENST00000908575.1		c.365G>A	p.Cys122Tyr	missense	Exon 2 of 2	ENSP00000578634.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000352 AC: 1 AN: 28408

American (AMR) AF: 0.00 AC: 0 AN: 41348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24038

East Asian (EAS) AF: 0.00 AC: 0 AN: 37102

South Asian (SAS) AF: 0.00 AC: 0 AN: 79732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5268

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 897366

Other (OTH) AF: 0.00 AC: 0 AN: 52162

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		7.5
PROVEAN	Pathogenic	-9.1	D
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	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

Other links and lift over

dbSNP: rs782612038; hg19: chr10-47087148;