10-70255162-C-G

Variant names:

• chr10-70255162-C-G
• NM_022146.5:c.1088G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022146.5(NPFFR1):​c.1088G>C​(p.Arg363Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000432 in 1,390,484 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000043 (0 hom.)
• Consequence: NPFFR1 NM_022146.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.473

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2970866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPFFR1	NM_022146.5	c.1088G>C	p.Arg363Pro	missense_variant	Exon 4 of 4	ENST00000277942.7	NP_071429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPFFR1	ENST00000277942.7	c.1088G>C	p.Arg363Pro	missense_variant	Exon 4 of 4	5	NM_022146.5	ENSP00000277942.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000432 AC: 6 AN: 1390484 Hom.: 0 Cov.: 40 AF XY: 0.00000583 AC XY: 4 AN XY: 685952

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000371

Gnomad4 OTH exome AF: 0.0000346

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1088G>C (p.R363P) alteration is located in exon 4 (coding exon 4) of the NPFFR1 gene. This alteration results from a G to C substitution at nucleotide position 1088, causing the arginine (R) at amino acid position 363 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.087
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	2.9	M
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.90	P
Vest4		0.13
MutPred		0.31		Loss of MoRF binding (P = 0.0096);
MVP		0.84
MPC		1.4
ClinPred		0.94	D
GERP RS		5.0
Varity_R		0.45
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-72014918;