Variant 3-5172694-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018184.3(ARL8B):c.326A>G(p.Asn109Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ARL8B
NM_018184.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.08

Variant links:

Genes affected

ARL8B (HGNC:25564): (ADP ribosylation factor like GTPase 8B) Enables guanyl ribonucleotide binding activity and tubulin binding activity. Involved in several processes, including calcium ion regulated lysosome exocytosis; lysosomal transport; and vesicle fusion. Located in cytolytic granule membrane; midbody; and spindle midzone. Colocalizes with lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARL8B links:

ENSG00000233912 (HGNC:):

ENSG00000233912 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28458893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL8B	NM_018184.3 linkuse as main transcript	c.326A>G	p.Asn109Ser	missense_variant	4/7	ENST00000256496.8	NP_060654.1	Q9NVJ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL8B	ENST00000256496.8 linkuse as main transcript	c.326A>G	p.Asn109Ser	missense_variant	4/7	1	NM_018184.3	ENSP00000256496.3		Q9NVJ2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251064

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460246

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726418

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.326A>G (p.N109S) alteration is located in exon 4 (coding exon 4) of the ARL8B gene. This alteration results from a A to G substitution at nucleotide position 326, causing the asparagine (N) at amino acid position 109 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.077

T;T;.

Eigen

Benign

0.069

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

.;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

-0.020

N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.1

N;.;N

REVEL

Benign

0.15

Sift

Benign

0.79

T;.;T

Sift4G

Benign

0.65

T;T;T

Polyphen

0.11

B;B;.

Vest4

0.53

MutPred

0.31

Gain of phosphorylation at N109 (P = 0.0296);Gain of phosphorylation at N109 (P = 0.0296);Gain of phosphorylation at N109 (P = 0.0296);

MVP

0.59

MPC

1.1

ClinPred

0.30

GERP RS

5.5

Varity_R

0.25

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over