chr12-48939689-C-T

Position:

chr12-48939689-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001659.3(ARF3):c.350G>A(p.Arg117Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ARF3
NM_001659.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARF3	NM_001659.3 linkuse as main transcript	c.350G>A	p.Arg117Gln	missense_variant	4/5	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.350G>A	p.Arg117Gln	missense_variant	4/5	1	NM_001659.3	ENSP00000256682.4		P61204-1
ENSG00000272822	ENST00000398092.4 linkuse as main transcript	c.350G>A	p.Arg117Gln	missense_variant	4/5	3		ENSP00000438507.1		F5H423

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251462

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2024

The c.350G>A (p.R117Q) alteration is located in exon 4 (coding exon 3) of the ARF3 gene. This alteration results from a G to A substitution at nucleotide position 350, causing the arginine (R) at amino acid position 117 to be replaced by a glutamine (Q). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.32

.;T;.;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

T;.;D;D

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.55

D;D;D;D

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.92

.;L;.;L

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.2

D;D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Benign

0.066

T;T;T;T

Polyphen

0.15

.;B;.;B

Vest4

0.72

MutPred

0.43

Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);.;Gain of relative solvent accessibility (P = 0.1894);

MVP

0.58

MPC

1.5

ClinPred

0.25

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.59

gMVP

0.80

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

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