Variant chr12-48939041-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3

The NM_001659.3(ARF3):c.452G>A(p.Arg151His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ARF3
NM_001659.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

Variant links:

Genes affected

ARF3 (HGNC:654): (ADP ribosylation factor 3) ADP-ribosylation factor 3 (ARF3) is a member of the human ARF gene family. These genes encode small guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin and play a role in vesicular trafficking and as activators of phospholipase D. The gene products include 6 ARF proteins and 11 ARF-like proteins and constitute one family of the RAS superfamily. The ARF proteins are categorized as class I (ARF1, ARF2,and ARF3), class II (ARF4 and ARF5) and class III (ARF6) and members of each class share a common gene organization. [provided by RefSeq, Oct 2022]

ARF3 links:

ENSG00000272822 (HGNC:):

ENSG00000272822 links:

FKBP11 (HGNC:18624): (FKBP prolyl isomerase 11) FKBP11 belongs to the FKBP family of peptidyl-prolyl cis/trans isomerases, which catalyze the folding of proline-containing polypeptides. The peptidyl-prolyl isomerase activity of FKBP proteins is inhibited by the immunosuppressant compounds FK506 and rapamycin (Rulten et al., 2006 [PubMed 16596453]).[supplied by OMIM, Mar 2008]

FKBP11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ARF3. . Gene score misZ 2.8247 (greater than the threshold 3.09). Trascript score misZ 3.6833 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARF3	NM_001659.3 linkuse as main transcript	c.452G>A	p.Arg151His	missense_variant	5/5	ENST00000256682.9	NP_001650.1	P61204-1A0A024R0Y6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARF3	ENST00000256682.9 linkuse as main transcript	c.452G>A	p.Arg151His	missense_variant	5/5	1	NM_001659.3	ENSP00000256682.4		P61204-1
ENSG00000272822	ENST00000398092.4 linkuse as main transcript	c.384+614G>A		intron_variant		3		ENSP00000438507.1		F5H423

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Mar 13, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.33

.;T;.;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

D;.;D;D

M_CAP

Benign

0.083

MetaRNN

Pathogenic

0.82

D;D;D;D

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.2

.;M;.;M

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-4.9

D;D;D;D

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.069

T;T;T;T

Polyphen

0.85

.;P;.;P

Vest4

0.33, 0.44, 0.39

MutPred

0.73

.;Gain of catalytic residue at R149 (P = 0);.;Gain of catalytic residue at R149 (P = 0);

MVP

0.55

MPC

1.8

ClinPred

1.0

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.74

gMVP

0.84

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

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