10-46461765-G-C

Position:

• chr10-46461765-G-C

Variant summary

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

The NM_005972.6(NPY4R):​c.871C>G​(p.His291Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 1)
• Consequence: NPY4R NM_005972.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.421

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13985899).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY4R	NM_005972.6	c.871C>G	p.His291Asp	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.871C>G	p.His291Asp	missense_variant	3/3	1	NM_005972.6	ENSP00000363431.1
NPY4R	ENST00000612632.3	c.871C>G	p.His291Asp	missense_variant	2/2	1		ENSP00000480883.1
ENSG00000285402	ENST00000616785.1	n.254-14713G>C		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 1

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 1

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

Aug 12, 2024

The c.871C>G (p.H291D) alteration is located in exon 3 (coding exon 1) of the NPY4R gene. This alteration results from a C to G substitution at nucleotide position 871, causing the histidine (H) at amino acid position 291 to be replaced by an aspartic acid (D). 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	0.20
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.95
MetaRNN	Benign	0.14	T;T
PROVEAN	Benign	-1.3	N;.
Sift	Benign	0.64	T;.
Sift4G	Benign	0.56	T;T
Vest4		0.19
gMVP		0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-47087654;