NM_004311.4:c.264+2405C>A

Variant names:

• chr10-102696968-G-T
• rs7904252
• NM_004311.4:c.264+2405C>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.264+2405C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,940 control chromosomes in the GnomAD database, including 8,260 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 (8260 hom., cov: 31)
• Consequence: ARL3 NM_004311.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 14 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL3	NM_004311.4	c.264+2405C>A		intron_variant	Intron 3 of 5	ENST00000260746.6	NP_004302.1
ARL3	XM_017016260.2	c.264+2405C>A		intron_variant	Intron 3 of 5		XP_016871749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL3	ENST00000260746.6	c.264+2405C>A		intron_variant	Intron 3 of 5	1	NM_004311.4	ENSP00000260746.4

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48706 AN: 151822 Hom.: 8255 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.303

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.321 AC: 48729 AN: 151940 Hom.: 8260 Cov.: 31 AF XY: 0.317 AC XY: 23510 AN XY: 74250

African (AFR) AF: 0.374 AC: 15489 AN: 41432

American (AMR) AF: 0.262 AC: 4000 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1128 AN: 3468

East Asian (EAS) AF: 0.157 AC: 812 AN: 5176

South Asian (SAS) AF: 0.139 AC: 668 AN: 4822

European-Finnish (FIN) AF: 0.364 AC: 3836 AN: 10538

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21944 AN: 67926

Other (OTH) AF: 0.300 AC: 633 AN: 2108

Alfa AF: 0.313 Hom.: 20606

Bravo AF: 0.319

Asia WGS AF: 0.154 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.94
PhyloP100		0.20
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: rs7904252; hg19: chr10-104456725;