10-46462166-T-C

Variant names:

• chr10-46462166-T-C
• NM_005972.6:c.470A>G

Variant summary

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

The NM_005972.6(NPY4R):​c.470A>G​(p.Tyr157Cys) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.0000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPY4R NM_005972.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.90
• 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 0 ACMG points.

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.470A>G	p.Tyr157Cys	missense	Exon 3 of 3	NP_005963.4
	NPY4R	NM_001278794.2		c.470A>G	p.Tyr157Cys	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.470A>G	p.Tyr157Cys	missense	Exon 3 of 3	ENSP00000363431.1	P50391
	NPY4R	ENST00000612632.3	TSL:1	c.470A>G	p.Tyr157Cys	missense	Exon 2 of 2	ENSP00000480883.1	P50391
	NPY4R	ENST00000908575.1		c.470A>G	p.Tyr157Cys	missense	Exon 2 of 2	ENSP00000578634.1

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251492 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000159 AC: 1 AN: 627060 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 326144

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

African (AFR) AF: 0.00 AC: 0 AN: 15894

American (AMR) AF: 0.00 AC: 0 AN: 31376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16798

East Asian (EAS) AF: 0.00 AC: 0 AN: 32184

South Asian (SAS) AF: 0.00 AC: 0 AN: 55370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2608

European-Non Finnish (NFE) AF: 0.00000245 AC: 1 AN: 407748

Other (OTH) AF: 0.00 AC: 0 AN: 32282

⚠️ 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.: 18

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	Benign	0.11
BayesDel_noAF	Uncertain	0.010
CADD	Benign	21
DANN	Uncertain	1.0
MetaRNN	Uncertain	0.72	D
PhyloP100		5.9
PROVEAN	Pathogenic	-6.7	D
Sift	Benign	0.092	T
Sift4G	Benign	0.089	T
Vest4		0.68
gMVP		0.92

Splicing

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

Other links and lift over

hg19: chr10-47087253;