2-26310850-G-C

Position:

• chr2-26310850-G-C

Variant summary

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

The NM_001321971.2(ADGRF3):​c.2674C>G​(p.Pro892Ala) 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. 12/20 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)
• Consequence: ADGRF3 NM_001321971.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.645

Genes affected

ADGRF3 (HGNC:18989): (adhesion G protein-coupled receptor F3) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and cell surface receptor signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ADGRF3 (HGNC:):

SELENOI (HGNC:29361): (selenoprotein I) The multi-pass transmembrane protein encoded by this gene belongs to the CDP-alcohol phosphatidyltransferase class-I family. It catalyzes the transfer of phosphoethanolamine from CDP-ethanolamine to diacylglycerol to produce phosphatidylethanolamine, which is involved in the formation and maintenance of vesicular membranes, regulation of lipid metabolism, and protein folding. This protein is a selenoprotein, containing the rare selenocysteine (Sec) amino acid at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2016]

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=0.14088649).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRF3	NM_001321971.2	c.2674C>G	p.Pro892Ala	missense_variant	10/14	ENST00000651242.2	NP_001308900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRF3	ENST00000651242.2	c.2674C>G	p.Pro892Ala	missense_variant	10/14		NM_001321971.2	ENSP00000498434.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 31, 2023

The c.2878C>G (p.P960A) alteration is located in exon 11 (coding exon 11) of the ADGRF3 gene. This alteration results from a C to G substitution at nucleotide position 2878, causing the proline (P) at amino acid position 960 to be replaced by an alanine (A). 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	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	.;.;T
Eigen	Benign	-0.013
Eigen_PC	Benign	0.013
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.83	.;T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.89	T
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-5.9	D;D;D
REVEL	Benign	0.097
Sift	Uncertain	0.020	D;D;T
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.36	B;.;B
Vest4		0.18
MutPred		0.48		.;.;Loss of glycosylation at P960 (P = 0.0127);
MVP		0.32
MPC		0.44
ClinPred		0.77	D
GERP RS		5.8
Varity_R		0.19
gMVP		0.078

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: chr2-26533718;