rs12573077

Positions:

• chr10-102674873-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004311.4(ARL3):​c.*2021G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,864 control chromosomes in the GnomAD database, including 8,335 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8332 hom., cov: 31)
  • Exomes 𝑓: 0.56 (3 hom.)
• Consequence: ARL3 NM_004311.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

Genes affected

ARL3 (HGNC:694): (ADP ribosylation factor like GTPase 3) Enables GDP binding activity; GTP binding activity; and microtubule binding activity. Involved in several processes, including cilium assembly; protein localization to cilium; and small GTPase mediated signal transduction. Acts upstream of or within post-Golgi vesicle-mediated transport. Located in several cellular components, including microtubule cytoskeleton; midbody; and photoreceptor connecting cilium. Implicated in Joubert syndrome and retinitis pigmentosa 83. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL3	NM_004311.4	c.*2021G>T		3_prime_UTR_variant	6/6	ENST00000260746.6
ARL3	XM_017016260.2	c.*2021G>T		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL3	ENST00000260746.6	c.*2021G>T		3_prime_UTR_variant	6/6	1	NM_004311.4	P1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 48964 AN: 151730 Hom.: 8329 Cov.: 31

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.563 AC: 9 AN: 16 Hom.: 3 Cov.: 0 AF XY: 0.583 AC XY: 7 AN XY: 12

Gnomad4 NFE exome AF: 0.563

GnomAD4 genome AF: 0.323 AC: 48975 AN: 151848 Hom.: 8332 Cov.: 31 AF XY: 0.317 AC XY: 23514 AN XY: 74196

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.304

Alfa AF: 0.317 Hom.: 8539

Bravo AF: 0.322

Asia WGS AF: 0.160 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.7
DANN	Benign	0.69

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: rs12573077; hg19: chr10-104434630;