10-102696968-G-T

Position:

• chr10-102696968-G-T

Variant summary

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

The ENST00000260746.6(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 ENST00000260746.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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=-0.64).
• 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/exons	MANE	Protein	UniProt
ARL3	NM_004311.4	c.264+2405C>A		intron_variant		ENST00000260746.6	NP_004302.1
ARL3	XM_017016260.2	c.264+2405C>A		intron_variant			XP_016871749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL3	ENST00000260746.6	c.264+2405C>A		intron_variant		1	NM_004311.4	ENSP00000260746	P1

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

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.300

Alfa AF: 0.308 Hom.: 13544

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

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: rs7904252; hg19: chr10-104456725;