NM_000910.4:c.775T>G

Variant names:

• chr4-155214714-T-G
• rs1393348618
• NM_000910.4:c.775T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000910.4(NPY2R):​c.775T>G​(p.Tyr259Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y259H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NPY2R NM_000910.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26
• Publications: 0 publications found

Genes affected

NPY2R (HGNC:7957): (neuropeptide Y receptor Y2) Predicted to enable calcium channel regulator activity and neuropeptide Y receptor activity. Involved in cardiac left ventricle morphogenesis and outflow tract morphogenesis. Located in cilium. Implicated in Huntington's disease; morbid obesity; and obesity. Biomarker of peripheral artery disease and temporal lobe epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

MAP9-AS1 (HGNC:56110): (MAP9 antisense RNA 1)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34106463).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000910.4. 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
	NPY2R	NM_000910.4	MANE Select	c.775T>G	p.Tyr259Asp	missense	Exon 2 of 2	NP_000901.1	P49146
	NPY2R	NM_001370180.1		c.775T>G	p.Tyr259Asp	missense	Exon 2 of 2	NP_001357109.1	P49146
	NPY2R	NM_001375470.1		c.775T>G	p.Tyr259Asp	missense	Exon 2 of 2	NP_001362399.1	P49146

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY2R	ENST00000329476.4	TSL:1 MANE Select	c.775T>G	p.Tyr259Asp	missense	Exon 2 of 2	ENSP00000332591.3	P49146
	NPY2R	ENST00000506608.1	TSL:1	c.775T>G	p.Tyr259Asp	missense	Exon 2 of 2	ENSP00000426366.1	P49146
	MAP9-AS1	ENST00000630664.3	TSL:5	n.399+40430T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251432 AF XY: 0.00

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 AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.053
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.11
Sift	Benign	0.21	T
Sift4G	Benign	0.26	T
Polyphen		0.38	B
Vest4		0.57
MutPred		0.44		Gain of glycosylation at Y259 (P = 0.0254)
MVP		0.50
MPC		0.59
ClinPred		0.31	T
GERP RS		5.6
Varity_R		0.14
gMVP		0.80
Mutation Taster		=68/32	polymorphism

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: rs1393348618; hg19: chr4-156135866;