Variant 10-18674029-A-T 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_178815.5(ARL5B):c.385A>T(p.Met129Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,912 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ARL5B
NM_178815.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.24

Variant links:

Genes affected

ARL5B (HGNC:23052): (ADP ribosylation factor like GTPase 5B) ARL5B (ARL8) belongs to a family of proteins that are structurally similar to ADP-ribosylation factors (ARFs; see MIM 103180). ARLs and ARFs are part of the RAS superfamily of regulatory GTPases.[supplied by OMIM, Nov 2010]

ARL5B links:

Genome browser will be placed here

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=0.16737035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ARL5B	NM_178815.5 linkuse as main transcript	c.385A>T	p.Met129Leu	missense_variant	5/6	ENST00000377275.4
ARL5B	XM_005252400.2 linkuse as main transcript	c.301A>T	p.Met101Leu	missense_variant	4/5
ARL5B	XM_005252401.5 linkuse as main transcript	c.274A>T	p.Met92Leu	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL5B	ENST00000377275.4 linkuse as main transcript	c.385A>T	p.Met129Leu	missense_variant	5/6	1	NM_178815.5	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250386

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135374

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

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:

1460912

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726758

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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

Dec 11, 2023

The c.385A>T (p.M129L) alteration is located in exon 5 (coding exon 5) of the ARL5B gene. This alteration results from a A to T substitution at nucleotide position 385, causing the methionine (M) at amino acid position 129 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.33

Cadd

Benign

Dann

Benign

0.70

DEOGEN2

Benign

0.018

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.25

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.75

M_CAP

Benign

0.017

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.87

MutationAssessor

Benign

-1.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.20

REVEL

Uncertain

0.30

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.37

MutPred

0.53

Loss of methylation at K126 (P = 0.0594);

MVP

0.64

MPC

0.56

ClinPred

0.21

GERP RS

4.6

Varity_R

0.40

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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