11-69005504-G-C

Position:

• chr11-69005504-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000309099.7(MRGPRF):​c.806C>G​(p.Ala269Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRGPRF ENST00000309099.7 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.409

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]

ACMG classification

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=0.17656636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRGPRF	NM_145015.5	c.806C>G	p.Ala269Gly	missense_variant	3/3	ENST00000309099.7	NP_659452.3
MRGPRF	NM_001098515.2	c.806C>G	p.Ala269Gly	missense_variant	3/3		NP_001091985.1
MRGPRF	XM_017017170.2	c.806C>G	p.Ala269Gly	missense_variant	3/3		XP_016872659.1
MRGPRF	XM_024448339.2	c.806C>G	p.Ala269Gly	missense_variant	3/3		XP_024304107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRGPRF	ENST00000309099.7	c.806C>G	p.Ala269Gly	missense_variant	3/3	1	NM_145015.5	ENSP00000309782	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

MRGPRF-related condition Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 09, 2024

The MRGPRF c.806C>G variant is predicted to result in the amino acid substitution p.Ala269Gly. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;T
Eigen	Benign	0.095
Eigen_PC	Benign	0.029
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.78	T;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.090
Sift	Benign	0.40	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.99	D;D
Vest4		0.12
MutPred		0.36		Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);
MVP		0.31
MPC		1.3
ClinPred		0.62	D
GERP RS		3.4
Varity_R		0.048
gMVP		0.46

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: chr11-68772972;