Genetic Variant NPFFR1:p.Arg260Pro (chr10-70255471-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_022146.5(NPFFR1):c.779G>C(p.Arg260Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,114 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

NPFFR1
NM_022146.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.860

Publications

0 publications found

Variant links:

Genes affected

NPFFR1 (HGNC:17425): (neuropeptide FF receptor 1) Predicted to enable G protein-coupled receptor activity and peptide binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

NPFFR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.3474322).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022146.5. 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
	NPFFR1	NM_022146.5	MANE Select	c.779G>C	p.Arg260Pro	missense	Exon 4 of 4	NP_071429.1	Q9GZQ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPFFR1	ENST00000277942.7	TSL:5 MANE Select	c.779G>C	p.Arg260Pro	missense	Exon 4 of 4	ENSP00000277942.5	Q9GZQ6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000689

AC:

AN:

145156

AF XY:

0.0000128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000409

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.16e-7

AC:

AN:

1396114

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688454

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31544

American (AMR)

AF:

0.0000281

AC:

AN:

35616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25114

East Asian (EAS)

AF:

0.00

AC:

AN:

35682

South Asian (SAS)

AF:

0.00

AC:

AN:

79146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078054

Other (OTH)

AF:

0.00

AC:

AN:

57890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.090

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.42

M_CAP

Benign

0.067

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

PhyloP100

0.86

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.14

Sift

Benign

0.21

Sift4G

Benign

0.14

Polyphen

0.99

Vest4

0.15

MutPred

0.63

Loss of MoRF binding (P = 0.005)

MVP

0.68

MPC

1.4

ClinPred

0.54

GERP RS

2.9

Varity_R

0.39

gMVP

0.89

Mutation Taster

=78/22

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over