Variant 11-69005411-T-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_145015.5(MRGPRF):c.899A>G(p.Gln300Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,582,746 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

MRGPRF
NM_145015.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.228

Variant links:

Genes affected

MRGPRF (HGNC:24828): (MAS related GPR family member F) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in nuclear membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MRGPRF 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=0.08392796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRF	NM_145015.5 linkuse as main transcript	c.899A>G	p.Gln300Arg	missense_variant	3/3	ENST00000309099.7	NP_659452.3	Q96AM1A0A024R5F0
MRGPRF	NM_001098515.2 linkuse as main transcript	c.899A>G	p.Gln300Arg	missense_variant	3/3		NP_001091985.1	Q96AM1A0A024R5F0
MRGPRF	XM_017017170.2 linkuse as main transcript	c.899A>G	p.Gln300Arg	missense_variant	3/3		XP_016872659.1	Q96AM1A0A024R5F0
MRGPRF	XM_024448339.2 linkuse as main transcript	c.899A>G	p.Gln300Arg	missense_variant	3/3		XP_024304107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRGPRF	ENST00000309099.7 linkuse as main transcript	c.899A>G	p.Gln300Arg	missense_variant	3/3	1	NM_145015.5	ENSP00000309782.6		Q96AM1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000864

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

GnomAD3 exomes

AF:

0.0000306

AC:

AN:

196284

Hom.:

AF XY:

0.0000282

AC XY:

AN XY:

106206

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000102

Gnomad ASJ exome

AF:

0.000337

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000105

AC:

AN:

1430542

Hom.:

Cov.:

AF XY:

0.00000846

AC XY:

AN XY:

708840

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000990

Gnomad4 ASJ exome

AF:

0.000392

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000864

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

Bravo

AF:

0.0000302

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 20, 2023

The c.899A>G (p.Q300R) alteration is located in exon 3 (coding exon 2) of the MRGPRF gene. This alteration results from a A to G substitution at nucleotide position 899, causing the glutamine (Q) at amino acid position 300 to be replaced by an arginine (R). 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

0.13

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.0045

T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.72

T;.

M_CAP

Benign

0.0096

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.23

N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.090

N;N

REVEL

Benign

0.14

Sift

Benign

0.91

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.98

D;D

Vest4

0.054

MVP

0.40

MPC

1.3

ClinPred

0.27

GERP RS

2.9

Varity_R

0.066

gMVP

0.32

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

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