Genetic Variant NM_012097.4:c.29G>A (chr2-151828148-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012097.4(ARL5A):c.29G>A(p.Arg10Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0000014 ( 0 hom. )

Consequence

ARL5A
NM_012097.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.53

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22205034).

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.29G>A	p.Arg10Lys	missense	Exon 1 of 6	NP_036229.1	Q9Y689-1
ARL5A	NM_001037174.2		c.-64+237G>A		intron	N/A	NP_001032251.1	Q9Y689-2
ARL5A	NM_177985.3		c.-66+241G>A		intron	N/A	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.29G>A	p.Arg10Lys	missense	Exon 1 of 6	ENSP00000295087.8	Q9Y689-1
ENSG00000283228	ENST00000637559.1	TSL:5	n.*333-12949G>A		intron	N/A	ENSP00000489697.1	A0A1B0GTH0
ARL5A	ENST00000899624.1		c.29G>A	p.Arg10Lys	missense	Exon 1 of 6	ENSP00000569683.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457592

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725098

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33016

American (AMR)

AF:

0.00

AC:

AN:

44286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25992

East Asian (EAS)

AF:

0.00

AC:

AN:

38978

South Asian (SAS)

AF:

0.00

AC:

AN:

85916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110024

Other (OTH)

AF:

0.00

AC:

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

0.15

BayesDel_addAF

Benign

-0.0025

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.041

Eigen

Benign

-0.18

Eigen_PC

Benign

0.043

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.48

M_CAP

Benign

0.042

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

4.5

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.14

REVEL

Benign

0.21

Sift

Benign

0.38

Sift4G

Benign

0.91

Polyphen

0.0

Vest4

0.43

MutPred

0.37

Gain of methylation at R10 (P = 0.0144)

MVP

0.61

MPC

0.18

ClinPred

0.65

GERP RS

4.9

PromoterAI

-0.070

Neutral

(source)

Varity_R

0.38

gMVP

0.78

Mutation Taster

=42/58

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over