Genetic Variant ARL5A:p.Arg175Gln (chr2-151803292-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012097.4(ARL5A):c.524G>A(p.Arg175Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000718 in 1,612,718 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 1 hom. )

Consequence

ARL5A
NM_012097.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

Publications

0 publications found

Variant links:

Genes affected

ARL5A (HGNC:696): (ADP ribosylation factor like GTPase 5A) The protein encoded by this gene belongs to the ARF family of GTP-binding proteins. With its distinctive nuclear/nucleolar localization and interaction with HP1alpha, the protein is developmentally regulated and may play a role(s) in nuclear dynamics and/or signaling cascades during embryonic development. Alternative splicing results in multiple transcript variants encoding different isoforms. This gene has multiple pseudogenes. [provided by RefSeq, Jul 2008]

ARL5A links:

ENSG00000283228 (HGNC:):

ENSG00000283228 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05490467).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012097.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARL5A	NM_012097.4	MANE Select	c.524G>A	p.Arg175Gln	missense	Exon 6 of 6	NP_036229.1	Q9Y689-1
ARL5A	NM_001037174.2		c.413G>A	p.Arg138Gln	missense	Exon 6 of 6	NP_001032251.1	Q9Y689-2
ARL5A	NM_177985.3		c.413G>A	p.Arg138Gln	missense	Exon 6 of 6	NP_817114.2	Q9Y689-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARL5A	ENST00000295087.13	TSL:1 MANE Select	c.524G>A	p.Arg175Gln	missense	Exon 6 of 6	ENSP00000295087.8	Q9Y689-1
ARL5A	ENST00000899624.1		c.473G>A	p.Arg158Gln	missense	Exon 6 of 6	ENSP00000569683.1
ARL5A	ENST00000899623.1		c.440G>A	p.Arg147Gln	missense	Exon 5 of 5	ENSP00000569682.1

Frequencies

GnomAD3 genomes

AF:

0.000487

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000379

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000358

AC:

AN:

248652

AF XY:

0.000319

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000666

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000742

AC:

1084

AN:

1460508

Hom.:

Cov.:

AF XY:

0.000694

AC XY:

504

AN XY:

726666

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33446

American (AMR)

AF:

0.0000671

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.00

AC:

AN:

86184

European-Finnish (FIN)

AF:

0.000131

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.000932

AC:

1035

AN:

1110930

Other (OTH)

AF:

0.000514

AC:

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

139

186

232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000486

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41540

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000379

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000684

Hom.:

Bravo

AF:

0.000567

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000362

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000534

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

Eigen

Benign

-0.28

Eigen_PC

Benign

0.0088

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.031

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.68

MutationAssessor

Benign

-0.21

PhyloP100

7.6

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.66

REVEL

Uncertain

0.39

Sift

Benign

0.92

Sift4G

Benign

1.0

Polyphen

0.099

Vest4

0.47

MVP

0.78

MPC

0.75

ClinPred

0.031

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.51

gMVP

0.52

Mutation Taster

=47/53

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over