10-46462251-T-C

Position:

• chr10-46462251-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000374312.5(NPY4R):​c.385A>G​(p.Ile129Val) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPY4R ENST00000374312.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24122071).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY4R	NM_005972.6	c.385A>G	p.Ile129Val	missense_variant	3/3	ENST00000374312.5	NP_005963.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY4R	ENST00000374312.5	c.385A>G	p.Ile129Val	missense_variant	3/3	1	NM_005972.6	ENSP00000363431	P1
NPY4R	ENST00000612632.3	c.385A>G	p.Ile129Val	missense_variant	2/2	1		ENSP00000480883	P1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000141 AC: 16 AN: 1132958 Hom.: 0 Cov.: 16 AF XY: 0.0000157 AC XY: 9 AN XY: 571782

Gnomad4 AFR exome AF: 0.00

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: 0.0000193

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2023

The c.385A>G (p.I129V) alteration is located in exon 3 (coding exon 1) of the NPY4R gene. This alteration results from a A to G substitution at nucleotide position 385, causing the isoleucine (I) at amino acid position 129 to be replaced by a valine (V). 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	Benign	0.12
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Uncertain	0.99
MetaRNN	Benign	0.24	T;T
PROVEAN	Benign	-0.49	N;.
Sift	Benign	0.27	T;.
Sift4G	Benign	0.43	T;T
Vest4		0.20
gMVP		0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554989686; hg19: chr10-47087168;