10-102676884-C-T

Variant names:

• chr10-102676884-C-T
• rs8354
• NM_004311.4:c.*10G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004311.4(ARL3):​c.*10G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,613,432 control chromosomes in the GnomAD database, including 14,039 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 0.10 (1270 hom., cov: 32)
  • Exomes 𝑓: 0.11 (12769 hom.)
• Consequence: ARL3 NM_004311.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495
• Publications: 24 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Joubert syndrome 35

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

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Illumina
• 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=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL3	NM_004311.4	c.*10G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000260746.6	NP_004302.1
ARL3	XM_017016260.2	c.*10G>A		3_prime_UTR_variant	Exon 6 of 6		XP_016871749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL3	ENST00000260746.6	c.*10G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_004311.4	ENSP00000260746.4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15852 AN: 152128 Hom.: 1267 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.0635

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.0632

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0943

Gnomad OTH AF: 0.125

GnomAD2 exomes AF: 0.147 AC: 36931 AN: 251298 AF XY: 0.147

Gnomad AFR exome AF: 0.0519

Gnomad AMR exome AF: 0.245

Gnomad ASJ exome AF: 0.0651

Gnomad EAS exome AF: 0.417

Gnomad FIN exome AF: 0.0637

Gnomad NFE exome AF: 0.0874

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.106 AC: 155460 AN: 1461186 Hom.: 12769 Cov.: 31 AF XY: 0.110 AC XY: 80113 AN XY: 726926

African (AFR) AF: 0.0466 AC: 1560 AN: 33472

American (AMR) AF: 0.240 AC: 10730 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0619 AC: 1617 AN: 26124

East Asian (EAS) AF: 0.441 AC: 17513 AN: 39672

South Asian (SAS) AF: 0.241 AC: 20781 AN: 86232

European-Finnish (FIN) AF: 0.0638 AC: 3403 AN: 53364

Middle Eastern (MID) AF: 0.103 AC: 596 AN: 5766

European-Non Finnish (NFE) AF: 0.0832 AC: 92445 AN: 1111484

Other (OTH) AF: 0.113 AC: 6815 AN: 60368

GnomAD4 genome AF: 0.104 AC: 15873 AN: 152246 Hom.: 1270 Cov.: 32 AF XY: 0.109 AC XY: 8080 AN XY: 74432

African (AFR) AF: 0.0523 AC: 2175 AN: 41554

American (AMR) AF: 0.176 AC: 2691 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0635 AC: 220 AN: 3466

East Asian (EAS) AF: 0.420 AC: 2179 AN: 5182

South Asian (SAS) AF: 0.232 AC: 1120 AN: 4824

European-Finnish (FIN) AF: 0.0632 AC: 670 AN: 10600

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0943 AC: 6414 AN: 68004

Other (OTH) AF: 0.128 AC: 270 AN: 2110

Alfa AF: 0.103 Hom.: 4186

Bravo AF: 0.112

Asia WGS AF: 0.295 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.3
DANN	Benign	0.86
PhyloP100		-0.49
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: rs8354; hg19: chr10-104436641; COSMIC: COSV53300939;