chr12-48940113-G-GA

Position:

• chr12-48940113-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001659.3(ARF3):​c.149-7dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,600,482 control chromosomes in the GnomAD database, including 105,452 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (9109 hom., cov: 0)
  • Exomes 𝑓: 0.37 (96343 hom.)
• Consequence: ARF3 NM_001659.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0340

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]

ENSG00000272822 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-48940113-G-GA is Benign according to our data. Variant chr12-48940113-G-GA is described in ClinVar as [Benign]. Clinvar id is 1221010.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARF3	NM_001659.3	c.149-7dupT		splice_region_variant, intron_variant		ENST00000256682.9	NP_001650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARF3	ENST00000256682.9	c.149-7dupT		splice_region_variant, intron_variant		1	NM_001659.3	ENSP00000256682.4
ENSG00000272822	ENST00000398092.4	c.149-7dupT		splice_region_variant, intron_variant		3		ENSP00000438507.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49505 AN: 151552 Hom.: 9101 Cov.: 0

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.359

GnomAD3 exomes AF: 0.375 AC: 92553 AN: 246856 Hom.: 18221 AF XY: 0.367 AC XY: 49088 AN XY: 133588

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.540

Gnomad ASJ exome AF: 0.425

Gnomad EAS exome AF: 0.458

Gnomad SAS exome AF: 0.224

Gnomad FIN exome AF: 0.373

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.380

GnomAD4 exome AF: 0.367 AC: 532408 AN: 1448812 Hom.: 96343 Cov.: 32 AF XY: 0.364 AC XY: 262744 AN XY: 721064

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.422

Gnomad4 EAS exome AF: 0.467

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.381

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.327 AC: 49524 AN: 151670 Hom.: 9109 Cov.: 0 AF XY: 0.330 AC XY: 24469 AN XY: 74098

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.362

Alfa AF: 0.266 Hom.: 894

EpiCase AF: 0.386

EpiControl AF: 0.390

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 27, 2020

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs5798094; hg19: chr12-49333896;