10-70255022-C-T

Variant names:

• chr10-70255022-C-T
• rs773001467
• NM_022146.5:c.1228G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022146.5(NPFFR1):​c.1228G>A​(p.Gly410Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000155 in 1,289,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. G410C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: NPFFR1 NM_022146.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05203685).

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.1228G>A	p.Gly410Ser	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.1228G>A	p.Gly410Ser	missense	Exon 4 of 4	ENSP00000277942.5	Q9GZQ6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000155 AC: 2 AN: 1289284 Hom.: 0 Cov.: 39 AF XY: 0.00000319 AC XY: 2 AN XY: 627822

African (AFR) AF: 0.00 AC: 0 AN: 25476

American (AMR) AF: 0.00 AC: 0 AN: 19120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18132

East Asian (EAS) AF: 0.00 AC: 0 AN: 32766

South Asian (SAS) AF: 0.00 AC: 0 AN: 62162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4958

European-Non Finnish (NFE) AF: 0.00000193 AC: 2 AN: 1036444

Other (OTH) AF: 0.00 AC: 0 AN: 53338

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.89
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.031
Sift	Benign	0.22	T
Sift4G	Benign	0.30	T
Polyphen		0.0010	B
Vest4		0.062
MutPred		0.23		Loss of catalytic residue at G410 (P = 0.0083)
MVP		0.51
MPC		1.0
ClinPred		0.075	T
GERP RS		-0.51
Varity_R		0.058
gMVP		0.45
Mutation Taster		=92/8	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: rs773001467; hg19: chr10-72014778;