Genetic Variant ADGRF3:p.Ile936Phe (chr2-26310718-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001321971.2(ADGRF3):c.2806A>T(p.Ile936Phe) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I936V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

ADGRF3
NM_001321971.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.456

Publications

1 publications found

Variant links:

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 links:

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]

SELENOI Gene-Disease associations (from GenCC):

spastic paraplegia 81, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: G2P
neurodevelopmental disorder
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

SELENOI links:

LOC105374334 (HGNC:):

LOC105374334 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2740581).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321971.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRF3	NM_001321971.2	MANE Select	c.2806A>T	p.Ile936Phe	missense	Exon 10 of 14	NP_001308900.1	A0A494C083
ADGRF3	NM_001145168.1		c.3010A>T	p.Ile1004Phe	missense	Exon 11 of 13	NP_001138640.1	Q8IZF5-1
ADGRF3	NM_001145169.1		c.2803A>T	p.Ile935Phe	missense	Exon 10 of 13	NP_001138641.1	Q8IZF5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRF3	ENST00000651242.2	MANE Select	c.2806A>T	p.Ile936Phe	missense	Exon 10 of 14	ENSP00000498434.1	A0A494C083
ADGRF3	ENST00000311519.5	TSL:1	c.3010A>T	p.Ile1004Phe	missense	Exon 11 of 13	ENSP00000307831.1	Q8IZF5-1
ADGRF3	ENST00000447444.5	TSL:1	n.2413A>T		non_coding_transcript_exon	Exon 8 of 13	ENSP00000404775.1	Q8IZF5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

6.4

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.042

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.69

M_CAP

Benign

0.018

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.66

PhyloP100

-0.46

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.24

Sift

Benign

0.071

Sift4G

Uncertain

0.048

Polyphen

0.90

Vest4

0.34

MutPred

0.52

Loss of stability (P = 0.191)

MVP

0.15

MPC

0.14

ClinPred

0.58

GERP RS

-3.5

Varity_R

0.29

gMVP

0.18

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over