Variant 4-121340458-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198179.3(QRFPR):c.493A>G(p.Met165Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000917 in 1,613,964 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

QRFPR
NM_198179.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

Variant links:

Genes affected

QRFPR (HGNC:15565): (pyroglutamylated RFamide peptide receptor) Enables G protein-coupled receptor activity. Involved in G protein-coupled receptor signaling pathway. Predicted to be located in non-motile cilium. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

QRFPR links:

QRFPR (HGNC:):

QRFPR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023628354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QRFPR	NM_198179.3 linkuse as main transcript	c.493A>G	p.Met165Val	missense_variant	2/6	ENST00000394427.3	NP_937822.2	Q96P65
QRFPR	XM_017008693.3 linkuse as main transcript	c.493A>G	p.Met165Val	missense_variant	2/4		XP_016864182.1	F2Z3L3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
QRFPR	ENST00000394427.3 linkuse as main transcript	c.493A>G	p.Met165Val	missense_variant	2/6	1	NM_198179.3	ENSP00000377948.2	Q96P65
QRFPR	ENST00000512235.1 linkuse as main transcript	n.905A>G		non_coding_transcript_exon_variant	2/2	1
QRFPR	ENST00000334383.9 linkuse as main transcript	c.493A>G	p.Met165Val	missense_variant	2/6	2		ENSP00000335610.5	J3KNR3
QRFPR	ENST00000507331.5 linkuse as main transcript	n.493A>G		non_coding_transcript_exon_variant	2/7	2		ENSP00000423369.1	F2Z3L3

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000215

AC:

AN:

251016

Hom.:

AF XY:

0.000229

AC XY:

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.0000794

AC:

116

AN:

1461646

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00110

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:

0.0000468

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000210

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.000359

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.493A>G (p.M165V) alteration is located in exon 2 (coding exon 2) of the QRFPR gene. This alteration results from a A to G substitution at nucleotide position 493, causing the methionine (M) at amino acid position 165 to be replaced by a valine (V). 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

0.063

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.017

.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.0080

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

.;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.12

Sift

Benign

0.13

T;D

Sift4G

Benign

0.59

T;T

Polyphen

0.12

.;B

Vest4

0.25

MVP

0.34

MPC

0.70

ClinPred

0.049

GERP RS

5.3

Varity_R

0.50

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over