NM_012097.4:c.211G>C

Variant names:

• chr2-151814213-C-G
• rs1338396146
• NM_012097.4:c.211G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012097.4(ARL5A):​c.211G>C​(p.Glu71Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,454,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ARL5A NM_012097.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.86
• Publications: 0 publications found

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]

ENSG00000283228 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL5A	NM_012097.4	MANE Select	c.211G>C	p.Glu71Gln	missense	Exon 3 of 6	NP_036229.1	Q9Y689-1
	ARL5A	NM_001037174.2		c.100G>C	p.Glu34Gln	missense	Exon 3 of 6	NP_001032251.1	Q9Y689-2
	ARL5A	NM_177985.3		c.100G>C	p.Glu34Gln	missense	Exon 3 of 6	NP_817114.2	Q9Y689-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL5A	ENST00000295087.13	TSL:1 MANE Select	c.211G>C	p.Glu71Gln	missense	Exon 3 of 6	ENSP00000295087.8	Q9Y689-1
	ARL5A	ENST00000899624.1		c.244G>C	p.Glu82Gln	missense	Exon 4 of 6	ENSP00000569683.1
	ARL5A	ENST00000899623.1		c.211G>C	p.Glu71Gln	missense	Exon 3 of 5	ENSP00000569682.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000122 AC: 3 AN: 245690 AF XY: 0.00000752

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000905

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000275 AC: 4 AN: 1454880 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723820

African (AFR) AF: 0.00 AC: 0 AN: 33004

American (AMR) AF: 0.0000685 AC: 3 AN: 43770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39238

South Asian (SAS) AF: 0.00 AC: 0 AN: 85088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4632

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109828

Other (OTH) AF: 0.00 AC: 0 AN: 60026

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	-0.024	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.7	N
REVEL	Pathogenic	0.68
Sift	Benign	0.18	T
Sift4G	Benign	0.17	T
Polyphen		0.59	P
Vest4		0.86
MutPred		0.44		Gain of MoRF binding (P = 0.0575)
MVP		0.83
MPC		0.34
ClinPred		0.55	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.49
Mutation Taster		=12/88	disease causing

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

Other links and lift over

dbSNP: rs1338396146; hg19: chr2-152670727;