dbSNP rs12573077: ARL3:c.*2021G>T (chr10-102674873-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0470

Publications

23 publications found

Variant links:

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

ARL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL3	NM_004311.4 link	c.*2021G>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000260746.6	NP_004302.1	P36405
ARL3	XM_017016260.2 link	c.*2021G>T		3_prime_UTR_variant	Exon 6 of 6		XP_016871749.1	P36405

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL3	ENST00000260746.6 link	c.*2021G>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_004311.4	ENSP00000260746.4		P36405

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

48964

AN:

151730

Hom.:

8329

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.583

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.563

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.323

AC:

48975

AN:

151848

Hom.:

8332

Cov.:

AF XY:

0.317

AC XY:

23514

AN XY:

74196

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.320

AC:

21742

AN:

67934

Other (OTH)

AF:

0.304

AC:

640

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1664

3328

4993

6657

8321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.7

(source)

DANN

Benign

0.69

PhyloP100

-0.047

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over