chr2-151806859-C-A

Variant names:

• chr2-151806859-C-A
• rs2099830172
• NM_012097.4:c.453G>T

Variant summary

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

The NM_012097.4(ARL5A):​c.453G>T​(p.Gln151His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,020 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: 6.8e-7 (0 hom.)
• Consequence: ARL5A NM_012097.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• 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.453G>T	p.Gln151His	missense	Exon 5 of 6	NP_036229.1	Q9Y689-1
	ARL5A	NM_001037174.2		c.342G>T	p.Gln114His	missense	Exon 5 of 6	NP_001032251.1	Q9Y689-2
	ARL5A	NM_177985.3		c.342G>T	p.Gln114His	missense	Exon 5 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.453G>T	p.Gln151His	missense	Exon 5 of 6	ENSP00000295087.8	Q9Y689-1
	ARL5A	ENST00000899624.1		c.402G>T	p.Gln134His	missense	Exon 5 of 6	ENSP00000569683.1
	ARL5A	ENST00000899623.1		c.369G>T	p.Gln123His	missense	Exon 4 of 5	ENSP00000569682.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461020 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726810

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111680

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	Benign	0.20
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.63	N
PhyloP100		1.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.41
Sift	Benign	0.22	T
Sift4G	Benign	0.20	T
Polyphen		0.12	B
Vest4		0.70
MutPred		0.25		Loss of catalytic residue at Q151 (P = 0.0071)
MVP		0.68
MPC		0.29
ClinPred		0.56	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.54
gMVP		0.55
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs2099830172; hg19: chr2-152663373;