NM_022146.5:c.1112G>T

Variant names:

• chr10-70255138-C-A
• rs1191374740
• NM_022146.5:c.1112G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022146.5(NPFFR1):​c.1112G>T​(p.Arg371Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPFFR1 NM_022146.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.815
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2405015).

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.1112G>T	p.Arg371Leu	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.1112G>T	p.Arg371Leu	missense	Exon 4 of 4	ENSP00000277942.5	Q9GZQ6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1377822 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 678610

African (AFR) AF: 0.00 AC: 0 AN: 30958

American (AMR) AF: 0.00 AC: 0 AN: 34130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23890

East Asian (EAS) AF: 0.00 AC: 0 AN: 35544

South Asian (SAS) AF: 0.00 AC: 0 AN: 76684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5296

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072430

Other (OTH) AF: 0.00 AC: 0 AN: 57266

GnomAD4 genome Cov.: 32

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	0.15
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.81
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.010	D
Polyphen		0.54	P
Vest4		0.27
MutPred		0.41		Loss of MoRF binding (P = 0.0369)
MVP		0.80
MPC		1.9
ClinPred		0.93	D
GERP RS		3.1
Varity_R		0.15
gMVP		0.79
Mutation Taster		=83/17	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: rs1191374740; hg19: chr10-72014894;