Variant 3-5122538-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018184.3(ARL8B):c.73C>A(p.Leu25Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,612,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ARL8B
NM_018184.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.41

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17784837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL8B	NM_018184.3 linkuse as main transcript	c.73C>A	p.Leu25Ile	missense_variant	1/7	ENST00000256496.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL8B	ENST00000256496.8 linkuse as main transcript	c.73C>A	p.Leu25Ile	missense_variant	1/7	1	NM_018184.3	P1	Q9NVJ2-1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000891

AC:

AN:

246896

Hom.:

AF XY:

0.0000448

AC XY:

AN XY:

134034

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000559

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:

0.000497

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1460538

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726582

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000583

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:

0.000116

GnomAD4 genome

AF:

0.000171

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000127

Hom.:

Bravo

AF:

0.000276

ExAC

AF:

0.000132

AC:

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 14, 2023

The c.73C>A (p.L25I) alteration is located in exon 1 (coding exon 1) of the ARL8B gene. This alteration results from a C to A substitution at nucleotide position 73, causing the leucine (L) at amino acid position 25 to be replaced by an isoleucine (I). 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

0.25

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.13

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.083

T;T;.

Eigen

Benign

0.060

Eigen_PC

Benign

0.084

FATHMM_MKL

Uncertain

0.88

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Uncertain

0.27

MutationAssessor

Benign

1.1

L;L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.5

N;.;N

REVEL

Uncertain

0.61

Sift

Benign

0.18

T;.;T

Sift4G

Benign

0.069

T;T;T

Polyphen

0.27

B;B;.

Vest4

0.57

MutPred

0.48

Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);

MVP

0.66

MPC

2.5

ClinPred

0.17

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.60

gMVP

0.89

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

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