Variant 11-69005597-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.713A>G(p.Asn238Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000632 in 1,423,898 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: not found (cov: 33)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

MRGPRF
NM_145015.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.799

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:

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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=0.10833481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRF	NM_145015.5 linkuse as main transcript	c.713A>G	p.Asn238Ser	missense_variant	3/3	ENST00000309099.7	NP_659452.3	Q96AM1A0A024R5F0
MRGPRF	NM_001098515.2 linkuse as main transcript	c.713A>G	p.Asn238Ser	missense_variant	3/3		NP_001091985.1	Q96AM1A0A024R5F0
MRGPRF	XM_017017170.2 linkuse as main transcript	c.713A>G	p.Asn238Ser	missense_variant	3/3		XP_016872659.1	Q96AM1A0A024R5F0
MRGPRF	XM_024448339.2 linkuse as main transcript	c.713A>G	p.Asn238Ser	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.713A>G	p.Asn238Ser	missense_variant	3/3	1	NM_145015.5	ENSP00000309782.6		Q96AM1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000535

AC:

AN:

186954

Hom.:

AF XY:

0.00

AC XY:

AN XY:

100020

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000410

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000632

AC:

AN:

1423898

Hom.:

Cov.:

AF XY:

0.00000993

AC XY:

AN XY:

704648

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:

0.000111

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000167

AC:

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 01, 2023

The c.713A>G (p.N238S) 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 713, causing the asparagine (N) at amino acid position 238 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0075

T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.71

T;.

M_CAP

Benign

0.028

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.2

L;L

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.10

Sift

Benign

0.43

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0070

B;B

Vest4

0.088

MutPred

0.74

Gain of disorder (P = 0.0506);Gain of disorder (P = 0.0506);

MVP

0.47

MPC

0.36

ClinPred

0.037

GERP RS

1.4

Varity_R

0.020

gMVP

0.64

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