2-26311030-C-T

Position:

chr2-26311030-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001321971.2(ADGRF3):c.2494G>A(p.Val832Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,611,650 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 20 hom. )

Consequence

ADGRF3
NM_001321971.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.592

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:

ADGRF3 (HGNC:):

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 2-26311030-C-T is Benign according to our data. Variant chr2-26311030-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650742.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRF3	NM_001321971.2 linkuse as main transcript	c.2494G>A	p.Val832Ile	missense_variant	10/14	ENST00000651242.2	NP_001308900.1	Q8IZF5A0A494C083

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRF3	ENST00000651242.2 linkuse as main transcript	c.2494G>A	p.Val832Ile	missense_variant	10/14		NM_001321971.2	ENSP00000498434.1		A0A494C083

Frequencies

GnomAD3 genomes

AF:

0.00292

AC:

444

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00227

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00440

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00330

AC:

810

AN:

245340

Hom.:

AF XY:

0.00346

AC XY:

459

AN XY:

132634

show subpopulations

Gnomad AFR exome

AF:

0.000648

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.000910

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00198

Gnomad FIN exome

AF:

0.00500

Gnomad NFE exome

AF:

0.00497

Gnomad OTH exome

AF:

0.00416

GnomAD4 exome

AF:

0.00345

AC:

5040

AN:

1459318

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

2498

AN XY:

725718

show subpopulations

Gnomad4 AFR exome

AF:

0.000629

Gnomad4 AMR exome

AF:

0.00189

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00194

Gnomad4 FIN exome

AF:

0.00556

Gnomad4 NFE exome

AF:

0.00386

Gnomad4 OTH exome

AF:

0.00237

GnomAD4 genome

AF:

0.00291

AC:

444

AN:

152332

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

209

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.00440

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00410

Hom.:

Bravo

AF:

0.00250

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00356

AC:

432

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

ADGRF3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.0025

.;.;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.66

.;T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0053

T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.28

PROVEAN

Benign

0.13

N;N;N

REVEL

Benign

0.047

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.42

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.065

MVP

0.055

MPC

0.092

ClinPred

0.0021

GERP RS

0.85

Varity_R

0.034

gMVP

0.066

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.39

Position offset: 3

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over