rs12573077

Variant names:

• chr10-102674873-C-A
• rs12573077
• NM_004311.4:c.*2021G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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]

ARL3 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 83

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Joubert syndrome 35

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Illumina, Orphanet
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004311.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL3	NM_004311.4	MANE Select	c.*2021G>T		3_prime_UTR	Exon 6 of 6	NP_004302.1	P36405

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL3	ENST00000260746.6	TSL:1 MANE Select	c.*2021G>T		3_prime_UTR	Exon 6 of 6	ENSP00000260746.4	P36405
	ARL3	ENST00000901818.1		c.*2021G>T		3_prime_UTR	Exon 5 of 5	ENSP00000571877.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.563 AC: 9 AN: 16

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.393 AC: 16246 AN: 41372

American (AMR) AF: 0.258 AC: 3935 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3470

East Asian (EAS) AF: 0.172 AC: 889 AN: 5168

South Asian (SAS) AF: 0.143 AC: 688 AN: 4816

European-Finnish (FIN) AF: 0.331 AC: 3473 AN: 10498

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.320 AC: 21742 AN: 67934

Other (OTH) AF: 0.304 AC: 640 AN: 2108

Alfa AF: 0.319 Hom.: 12602

Bravo AF: 0.322

Asia WGS AF: 0.160 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.7
DANN	Benign	0.69
PhyloP100		-0.047
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12573077; hg19: chr10-104434630;