Variant 11-69005880-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_145015.5(MRGPRF):c.430T>C(p.Ser144Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000354 in 1,411,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

MRGPRF
NM_145015.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.849

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.959

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRF	NM_145015.5 link	c.430T>C	p.Ser144Pro	missense_variant	3/3	ENST00000309099.7	NP_659452.3	Q96AM1A0A024R5F0
MRGPRF	NM_001098515.2 link	c.430T>C	p.Ser144Pro	missense_variant	3/3		NP_001091985.1	Q96AM1A0A024R5F0
MRGPRF	XM_017017170.2 link	c.430T>C	p.Ser144Pro	missense_variant	3/3		XP_016872659.1	Q96AM1A0A024R5F0
MRGPRF	XM_024448339.2 link	c.430T>C	p.Ser144Pro	missense_variant	3/3		XP_024304107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRGPRF	ENST00000309099.7 link	c.430T>C	p.Ser144Pro	missense_variant	3/3	1	NM_145015.5	ENSP00000309782.6		Q96AM1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000354

AC:

AN:

1411966

Hom.:

Cov.:

AF XY:

0.00000573

AC XY:

AN XY:

697536

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:

0.00000459

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 05, 2023

The c.430T>C (p.S144P) alteration is located in exon 3 (coding exon 2) of the MRGPRF gene. This alteration results from a T to C substitution at nucleotide position 430, causing the serine (S) at amino acid position 144 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

Pathogenic

0.75

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.10

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;T

Eigen

Benign

0.18

Eigen_PC

Benign

-0.038

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.69

T;.

M_CAP

Uncertain

0.094

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Uncertain

-0.15

MutationAssessor

Pathogenic

3.2

M;M

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-4.7

D;D

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;D

Vest4

0.69

MutPred

0.85

Loss of MoRF binding (P = 0.0651);Loss of MoRF binding (P = 0.0651);

MVP

0.47

MPC

1.4

ClinPred

0.99

GERP RS

4.9

Varity_R

0.76

gMVP

0.92

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over