rs72811754

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -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. 14/23 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

Publications

4 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: Likely_benign. The variant received -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 VariationId is 2650742.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

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.2494G>A	p.Val832Ile	missense	Exon 10 of 14	NP_001308900.1	A0A494C083
ADGRF3	NM_001145168.1		c.2698G>A	p.Val900Ile	missense	Exon 11 of 13	NP_001138640.1	Q8IZF5-1
ADGRF3	NM_001145169.1		c.2491G>A	p.Val831Ile	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.2494G>A	p.Val832Ile	missense	Exon 10 of 14	ENSP00000498434.1	A0A494C083
ADGRF3	ENST00000311519.5	TSL:1	c.2698G>A	p.Val900Ile	missense	Exon 11 of 13	ENSP00000307831.1	Q8IZF5-1
ADGRF3	ENST00000447444.5	TSL:1	n.2101G>A		non_coding_transcript_exon	Exon 8 of 13	ENSP00000404775.1	Q8IZF5-2

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

GnomAD2 exomes

AF:

0.00330

AC:

810

AN:

245340

AF XY:

0.00346

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 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

African (AFR)

AF:

0.000629

AC:

AN:

33388

American (AMR)

AF:

0.00189

AC:

AN:

44420

Ashkenazi Jewish (ASJ)

AF:

0.00119

AC:

AN:

26052

East Asian (EAS)

AF:

0.00

AC:

AN:

39568

South Asian (SAS)

AF:

0.00194

AC:

166

AN:

85662

European-Finnish (FIN)

AF:

0.00556

AC:

296

AN:

53240

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00386

AC:

4292

AN:

1110926

Other (OTH)

AF:

0.00237

AC:

143

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

321

642

963

1284

1605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00291

AC:

444

AN:

152332

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

209

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41586

American (AMR)

AF:

0.00261

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00228

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00405

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00440

AC:

299

AN:

68022

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00393

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.0025

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.66

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0053

MetaSVM

Benign

-0.99

PhyloP100

-0.59

PrimateAI

Benign

0.28

PROVEAN

Benign

0.13

REVEL

Benign

0.047

Sift

Benign

1.0

Sift4G

Benign

0.42

Polyphen

0.0010

Vest4

0.065

MVP

0.055

MPC

0.092

ClinPred

0.0021

GERP RS

0.85

Varity_R

0.034

gMVP

0.066

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over