rs753855623

Variant names:

• chr10-70255495-C-A
• rs753855623
• NM_022146.5:c.755G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-70255495-C-A
• chr10-70255495-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_022146.5(NPFFR1):​c.755G>T​(p.Gly252Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000588 in 1,547,470 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G252E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: NPFFR1 NM_022146.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.07
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019821644).

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.755G>T	p.Gly252Val	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.755G>T	p.Gly252Val	missense	Exon 4 of 4	ENSP00000277942.5	Q9GZQ6

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 151958 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000523 AC: 76 AN: 145384 AF XY: 0.000447

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00307

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: 0.000239

GnomAD4 exome AF: 0.0000580 AC: 81 AN: 1395512 Hom.: 0 Cov.: 39 AF XY: 0.0000567 AC XY: 39 AN XY: 687858

African (AFR) AF: 0.00 AC: 0 AN: 31484

American (AMR) AF: 0.00219 AC: 78 AN: 35548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25076

East Asian (EAS) AF: 0.00 AC: 0 AN: 35636

South Asian (SAS) AF: 0.00 AC: 0 AN: 79076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47756

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077414

Other (OTH) AF: 0.0000519 AC: 3 AN: 57834

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 151958 Hom.: 0 Cov.: 32 AF XY: 0.0000674 AC XY: 5 AN XY: 74212

African (AFR) AF: 0.00 AC: 0 AN: 41380

American (AMR) AF: 0.000655 AC: 10 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000196

ExAC AF: 0.0000182 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.58
DANN	Benign	0.75
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	2.0	M
PhyloP100		-1.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.10
Sift	Benign	0.15	T
Sift4G	Benign	0.11	T
Polyphen		0.12	B
Vest4		0.090
MutPred		0.45		Loss of disorder (P = 0.0429)
MVP		0.52
MPC		1.3
ClinPred		0.061	T
GERP RS		-7.8
Varity_R		0.063
gMVP		0.42
Mutation Taster		=95/5	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: rs753855623; hg19: chr10-72015251;