11-69005880-A-G

Variant summary

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

The NM_145015.5(MRGPRF):ā€‹c.430T>Cā€‹(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 (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000035 ( 0 hom. )

Consequence

MRGPRF
NM_145015.5 missense

Scores

6
7
6

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]

Genome browser will be placed here

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
MRGPRFNM_145015.5 linkc.430T>C p.Ser144Pro missense_variant 3/3 ENST00000309099.7 NP_659452.3 Q96AM1A0A024R5F0
MRGPRFNM_001098515.2 linkc.430T>C p.Ser144Pro missense_variant 3/3 NP_001091985.1 Q96AM1A0A024R5F0
MRGPRFXM_017017170.2 linkc.430T>C p.Ser144Pro missense_variant 3/3 XP_016872659.1 Q96AM1A0A024R5F0
MRGPRFXM_024448339.2 linkc.430T>C p.Ser144Pro missense_variant 3/3 XP_024304107.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MRGPRFENST00000309099.7 linkc.430T>C p.Ser144Pro missense_variant 3/31 NM_145015.5 ENSP00000309782.6 Q96AM1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000354
AC:
5
AN:
1411966
Hom.:
0
Cov.:
30
AF XY:
0.00000573
AC XY:
4
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.:
33

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 submitterclinical testingAmbry GeneticsOct 05, 2023The 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
D
BayesDel_noAF
Uncertain
0.10
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T;T
Eigen
Benign
0.18
Eigen_PC
Benign
-0.038
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.69
T;.
M_CAP
Uncertain
0.094
D
MetaRNN
Pathogenic
0.96
D;D
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Pathogenic
3.2
M;M
PrimateAI
Uncertain
0.77
T
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
D
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.

Other links and lift over

hg19: chr11-68773348; API