Variant 5-176368854-G-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_173664.6(ARL10):c.433G>A(p.Glu145Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,461,802 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: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ARL10
NM_173664.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

Variant links:

Genes affected

ARL10 (HGNC:22042): (ADP ribosylation factor like GTPase 10) Predicted to enable GTP binding activity and GTPase activity. [provided by Alliance of Genome Resources, Apr 2022]

ARL10 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=0.13244489).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL10	NM_173664.6 linkuse as main transcript	c.433G>A	p.Glu145Lys	missense_variant	3/4	ENST00000310389.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ARL10	ENST00000310389.6 linkuse as main transcript	c.433G>A	p.Glu145Lys	missense_variant	3/4	2	NM_173664.6	P1
ARL10	ENST00000514533.1 linkuse as main transcript	c.7G>A	p.Glu3Lys	missense_variant	1/2	3
ARL10	ENST00000507151.1 linkuse as main transcript	n.92G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250950

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727206

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jul 13, 2021

The c.433G>A (p.E145K) alteration is located in exon 3 (coding exon 3) of the ARL10 gene. This alteration results from a G to A substitution at nucleotide position 433, causing the glutamic acid (E) at amino acid position 145 to be replaced by a lysine (K). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Benign

0.041

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.74

M_CAP

Benign

0.0085

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.28

MutationTaster

Benign

0.80

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.63

REVEL

Benign

0.14

Sift

Benign

0.97

Sift4G

Benign

0.82

Polyphen

0.49

Vest4

0.30

MutPred

0.50

Gain of methylation at E145 (P = 0.0126);

MVP

0.80

MPC

1.3

ClinPred

0.32

GERP RS

4.3

Varity_R

0.052

gMVP

0.56

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