chr2-151828148-C-T

Variant names:

• chr2-151828148-C-T
• rs2099833344
• NM_012097.4:c.29G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ARL5A NM_012097.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53

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

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=0.22205034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL5A	NM_012097.4	c.29G>A	p.Arg10Lys	missense_variant	Exon 1 of 6	ENST00000295087.13	NP_036229.1
ARL5A	NM_001037174.2	c.-64+237G>A		intron_variant	Intron 1 of 5		NP_001032251.1
ARL5A	NM_177985.3	c.-66+241G>A		intron_variant	Intron 1 of 5		NP_817114.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL5A	ENST00000295087.13	c.29G>A	p.Arg10Lys	missense_variant	Exon 1 of 6	1	NM_012097.4	ENSP00000295087.8
ENSG00000283228	ENST00000637559.1	n.*333-12949G>A		intron_variant	Intron 10 of 11	5		ENSP00000489697.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457592 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725098

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.29G>A (p.R10K) alteration is located in exon 1 (coding exon 1) of the ARL5A gene. This alteration results from a G to A substitution at nucleotide position 29, causing the arginine (R) at amino acid position 10 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	Benign	0.15
BayesDel_addAF	Benign	-0.0025	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.043
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.21
Sift	Benign	0.38	T
Sift4G	Benign	0.91	T
Polyphen		0.0	B
Vest4		0.43
MutPred		0.37		Gain of methylation at R10 (P = 0.0144);
MVP		0.61
MPC		0.18
ClinPred		0.65	D
GERP RS		4.9
Varity_R		0.38
gMVP		0.78

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

LitVar

Other links and lift over

dbSNP: rs2099833344; hg19: chr2-152684662;