NM_022146.5:c.779G>A

Variant names:

• chr10-70255471-C-T
• rs548531274
• NM_022146.5:c.779G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_022146.5(NPFFR1):​c.779G>A​(p.Arg260Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000172 in 1,396,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R260P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: NPFFR1 NM_022146.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.860
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15006357).

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>A	p.Arg260Gln	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>A	p.Arg260Gln	missense	Exon 4 of 4	ENSP00000277942.5	Q9GZQ6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000620 AC: 9 AN: 145156 AF XY: 0.0000511

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000172 AC: 24 AN: 1396114 Hom.: 0 Cov.: 40 AF XY: 0.0000203 AC XY: 14 AN XY: 688454

African (AFR) AF: 0.0000634 AC: 2 AN: 31544

American (AMR) AF: 0.00 AC: 0 AN: 35616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25114

East Asian (EAS) AF: 0.00 AC: 0 AN: 35682

South Asian (SAS) AF: 0.000253 AC: 20 AN: 79146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078054

Other (OTH) AF: 0.0000345 AC: 2 AN: 57890

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000345 AC: 2

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.83
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.86
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.14
Sift	Benign	0.46	T
Sift4G	Benign	0.45	T
Polyphen		0.97	D
Vest4		0.13
MutPred		0.48		Loss of MoRF binding (P = 0.0311)
MVP		0.57
MPC		1.5
ClinPred		0.063	T
GERP RS		2.9
Varity_R		0.063
gMVP		0.53
Mutation Taster		=86/14	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: rs548531274; hg19: chr10-72015227;