Variant 4-121332851-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198179.3(QRFPR):c.767T>G(p.Ile256Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,830 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

QRFPR
NM_198179.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.09

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2430234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QRFPR	NM_198179.3 linkuse as main transcript	c.767T>G	p.Ile256Ser	missense_variant	4/6	ENST00000394427.3	NP_937822.2	Q96P65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
QRFPR	ENST00000394427.3 linkuse as main transcript	c.767T>G	p.Ile256Ser	missense_variant	4/6	1	NM_198179.3	ENSP00000377948.2	Q96P65
QRFPR	ENST00000334383.9 linkuse as main transcript	c.684+83T>G		intron_variant		2		ENSP00000335610.5	J3KNR3
QRFPR	ENST00000507331.5 linkuse as main transcript	n.*325T>G		non_coding_transcript_exon_variant	5/7	2		ENSP00000423369.1	F2Z3L3
QRFPR	ENST00000507331.5 linkuse as main transcript	n.*325T>G		3_prime_UTR_variant	5/7	2		ENSP00000423369.1	F2Z3L3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461592

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727126

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

0.0050

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

Eigen

Benign

-0.13

Eigen_PC

Benign

0.063

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.054

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.23

REVEL

Uncertain

0.33

Sift

Benign

0.098

Sift4G

Uncertain

0.0090

Polyphen

0.36

Vest4

0.42

MutPred

0.53

Gain of disorder (P = 3e-04);

MVP

0.72

MPC

0.030

ClinPred

0.77

GERP RS

5.0

Varity_R

0.18

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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